The paper describes a new synthetic method for the 1,5-methanoazocino [4,3-b]indole. Starting from 2,3,4,9-tetrahydrospiro[1H-carbazole-1,2'-[1,3]dithiolan]-4(9H)-one I with (1,3-dithiolan-2-yl)methanamine, reduction of imine II with NaBH4 yielded to the amine and benzoylation, N-((1,3-dithiolan-2-yl)methyl)-N-(2,3,4,9-tetrahydrospiro[carbazole-1,2'-[1,3]dithiolan]-4-yl)benzamide III. Compounds IV and V were completed through several steps from III. The resulting structure V underwent an intramolecular aldol reaction using NaH as a base for the cyclization of 2-benzoyle-4-hydroxy-1,2,3,4,5,7-hexehydro-1,5-methanoazocino[4,3-b]indole-6-one VI, which represents the tetracyclic skeleton of Strychnos alkaloids. Besides, quantum chemical computations were conducted on compounds I-VI. Regarding structural parameters and spectroscopic characterization, the experimental and computational data were found to be in good agreement. Also, ADMET, bioavailability, and drug-likeness properties of the data set were determined to provide comprehensive information on structure-activity relationships. The interactions of I-VI against DNA gyrase of E. coli, CYP51 from Candida glabrata, and leukemia inhibitory factor were evaluated with molecular docking for foresight into the possible bioactivities. This comprehensive work hopefully to provide the structural, physical, and chemical properties, which would be important to optimizing the related properties of the molecular systems for biomedical purposes.

A series of dinuclear Pd(II)-PEPPSI type complexes with N-heterocyclic carbene (NHC) ligand were synthesized and characterized by 1 H and 13 C NMR spectroscopy, IR, elemental analyses, and mass spectrometry. These dinuclear PEPPSI type NHC-palladium complexes exhibited efficient catalytic activities for the direct arylation reactions of 3,5-dimethylisoxazole, 1-methyl-2-pyrrolecarboxaldehyde with aryl bromide. Additionally, the antiproliferative activities of three palladium(II) complexes 2a, 2b and 2c were evaluated using the MTT assay in two cancer cell lines (A549 and HeLa) and one non-tumorigenic cell line (hTERT). Complexes 2a-2c were evaluated for antiproliferative activity, revealing that 2a exhibited the highest potency and selectivity (IC50 = 13.4-12.6 mu M; SI = 6.5-6.9) against A549 and HeLa cells. Complex 2b showed moderate activity and 2c the weakest. The elevated IC50 values in hTERT cells highlight the tumor selectivity of these Pd complexes, positioning 2a as the most promising anticancer candidate. Furthermore, the quantum mechanical computations of the Pd-complexes (2a-2c) were performed at HF/6-31G(d,p)/LANL2DZ, for structural optimization and confirmations by no imaginary frequency, following the IRC "Intrinsic Reaction Coordinate" computations. Then, the FMO analyses of the complexes were conducted withthe same theory to determine the global reactivity directions and possible sites. Additionally, molecular docking analyses were performed against the crystal structures of VEGFR2, estrogen receptor, and ERK2. 2b has the best binding affinity against VEGFR2 with-8.46 kcal/mol, while 2c has remarkable interactions against estrogen receptor and ERK2 with-9.27 kcal/mol and-7.05 kcal/ mol binding values, respectively. Also, the interactions between DNA and the molecules were analyzed.

ABSTRACT Theophylline, a naturally occurring xanthine derivative with well‐established pharmaceutical applications, has recently emerged as an attractive scaffold in coordination chemistry and catalysis because of its unique heterocyclic structure and donor properties. In this study, two novel N(7)‐substituted theophylline derivatives, namely 1,3‐dimethyl‐7‐((2,3,5,6‐tetramethyl)benzyl)‐3,7‐dihydro‐1 H ‐purine‐2,6‐dione and 1,3‐dimethyl‐7‐((2,3,4,5,6‐pentamethyl)benzyl)‐3,7‐dihydro‐1 H ‐purine‐2,6‐dione, were synthesized and comprehensively characterized by spectroscopic methods, single‐crystal x‐ray diffraction analysis, and density functional theory (DFT) calculations. Structural and theoretical investigations were carried out to evaluate their electronic features, coordination behavior, and potential interaction sites. For the first time, these theophylline‐based heterocyclic compounds were employed as ligand‐like components in in situ generated palladium catalytic systems for C─H bond activation reactions. The catalytic results demonstrated that the N(7)‐substituted theophylline framework effectively stabilizes palladium intermediates and promotes selective C─H functionalization under mild reaction conditions. DFT studies further revealed that the nitrogen donor centers of the theophylline scaffold play an important role in tuning the electronic properties and reactivity of the palladium species. In addition, frontier molecular orbital analyses, including HOMO–LUMO energy levels and orbital localizations, provided insight into the possible coordination and interaction regions of the molecules. These findings establish N(7)‐substituted theophylline derivatives as a new class of ligand‐like scaffolds for Pd‐catalyzed C─H activation.

Schiff base ligand (H2L) and its metal complexes (Co(II) and Cu(II)) have been synthesized from the reaction between 2,3-dihydrobenzo[b][1,4]Dioxine-6,7-diamine and 4-(diethylamino)-2-hydroxybenzaldehyde. The ligand and its complexes were characterized using FTIR, UV-Vis, elemental (CHN) analysis and mass spectrometry methods. The antibacterial activity of the Schiff base ligand (H2L) and its complexes was evaluated against S. aureus and Escherichia coli strains. The complexes with Cu(II) and Co(II) showed MIC values of 23.7 +/- 0.2 mu g/ml and 22.9 +/- 0.1 mu g/ml, respectively, at a concentration of 100 mu g/ml, which were more favorable than the parent ligand. The antiproliferative activity of H2L and its Co(II) and Cu(II) metal complexes, have been evaluated using the MTT assay against human breast, lung, colorectal, and liver cancer cell lines. The Cu(II) complex showed the better anticancer activity against A549 (IC50= 16.12 +/- 5.48 & micro;g/mL), MCF-7 (IC50= 13.18 +/- 4.14 & micro;g/mL), HepG2 (IC50= 15.18 +/- 5.48 & micro;g/mL), and HCT116 (IC50= 17.11 +/- 3.18 & micro;g/mL) cell lines, with IC50 values significantly lower than those of the Co(II) complex and the parent ligand. Additionally, computational studies at the B3LYP/6-311G++(d,p) and LANL2DZ basis sets provided insights into the electronic properties of the compounds, supporting the experimental results. Schiff base ligand and its metal complexes have also been docked against VEGFR2, ERK2, DNA gyrase, and SarA proteins. Molecular docking studies of the Cu(II) complex revealed strong binding affinities with target proteins VEGFR2, ERK2, DNA gyrase and SarA proteins with binding energies of -6.55, -8.85, -8.38 and -6.80 kcal/mol, respectively.

Background/Objectives: Cutaneous leishmaniasis (CL) is a prevalent vector-borne disease characterized by a broad spectrum of clinical manifestations resulting from protozoan parasites belonging to the genus Leishmania. The challenges associated with the treatment of CL are attributable to various factors, including but not limited to: drug resistance, the adverse effects of conventional therapeutic interventions and the imperative for novel therapeutic alternatives to address the global health burden posed by this neglected tropical disease. Methods: In this study, The therapeutic efficacy of two silver(I)-N-heterocyclic carbene (NHC) complexes, namely chloro[1-methallyl-3-(2,4,6-trimethylbenzyl)-5,6-dimethylbenzimidazole-2-ylidene]silver(I) (2a) and chloro[1-methallyl-3-(4-chlorobenzyl)-5,6-dimethylbenzimidazole-2-ylidene]silver(I) (2b), was evaluated against promastigotes in vitro and in vivo in an experimentally induced CL model in Balb/c mice. Results: The findings of this study indicated that these compounds possess the potential to function as effective therapeutic agents, particularly in the treatment of CL. Subsequently, the silver(I) complexes were analyzed by means of molecular docking against LaGP63, LaARG, N-myristoyltransferase and farnesyl pyrophosphate synthase. Conclusions: According to the docking evaluations, complex 2a emerged as the most notable molecule in terms of its potential antileishmanial activity.

A new series of 5-mercapto-1,3,4-thiadiazol (SH-2NBA, SH-3NBA, and SH-4NBA), and 5-methylisoxazol (OX-2NBA, OX-3NBA, and OX-4NBA) bearing mercapto or methyl moieties were synthesized by the reaction of 2,3,4-nitrobenzoyl chloride with 5-amino-1,3,4-thiadiazole-2-thiol and 3-amino-5-methylisoxazole in the presence of toluene-TEA. Their structures were characterized with H-1 NMR, C-13 NMR, UV, and FT-IR. These compounds possess a broad variety of functional activities and have become the subject of considerable growing interest for designing synthesis. The quantum mechanical computations were performed at B3LYP/6-311G** level in both the gas and DMSO simulation environments, for structural and spectroscopic confirmation, then evaluation of the chemical reactivity behavior of the thiadiazol and oxazol isomers. The solubility in octanol and water, ADMET, and drug-likeness properties were elucidated to predict the possible pharmacokinetic profiles, drug-likeness properties, and bioavailability indexes, which would provide a deep insight into early-stage drug-design works. Additionally, BSA binding and DNA binding properties of the molecules were evaluated using spectrophotometric methods. BSA binding properties were analyzed by the Stern-Volmer method, while DNA binding analyses were performed by the Benesi-Hildebrand method. Additionally, the details of both BSA and DNA binding properties were evaluated using molecular docking methods.

In this study, two new ester-functionalized benzimidazolium salts were synthesized as N-heterocyclic carbene (NHC) ligand precursors, and four new ester-functionalized PEPPSI-type Pd-NHC complexes were subsequently prepared from these salts. The structural characterization of all newly synthesized compounds was accomplished by means of 1H NMR, 13C NMR and FT-IR spectroscopic techniques, and elemental analysis. Furthermore, the detailed structural elucidation of one of the palladium complexes (3b) was achieved through single-crystal X-ray diffraction (SC-XRD) analysis. The antimicrobial activities of the benzimidazolium salts and the PEPPSI-type Pd-NHC complexes were evaluated against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacterial strains, as well as the fungal strain Aspergillus niger. The antimicrobial test results were compared with those of reference drugs, and it was observed that PEPPSI-type Pd-NHC complexes exhibited activity similar to that of standard therapeutic agents under certain test conditions. Additionally, antimicrobial activity of both benzimidazolium salts and their PEPPSI-type Pd-NHC complexes were evaluated with molecular docking method against DNA Gyrase and SarA. According to the results, palladium complexes had better activity than the benzimidazolium salts, and the best interaction value was determined for complex 3b both against DNA Gyrase and SarA with -7.52 kcal/mol and -5.90 kcal/mol, respectively.

The synthesis and characterization of three novel PEPPSI-type complexes, dichloro[1-allyl-3-(2-methylbenzyl)benzimidazole-2-ylidene]pyridine palladium(II) (2a), dichloro[1-allyl-3-(2-chlorobenzyl)-benzimidazole-2ylidene]pyridine palladium(II) (2b) and dichloro[1-allyl-3-(3-methylbenzyl)-benzimidazole-2-ylidene]pyridine palladium(II) (2c) were carried out. The structure of the complexes was elucidated by elemental analysis, NMR and IR spectroscopy. In addition, the structure of complex 2c was confirmed through single-crystal X-ray diffraction. BSA and DNA binding properties of the designed complexes were evaluated spectroscopically by Benesi-Hildebrand method. According to both DNA- and BSA-binding experiments, 2b has the best binding affinity with 3.06x104 M- 1, and 2.5x104 M- 1, respectively. Also, the bindings of the complexes were also evaluated by molecular docking methods, which gave accordance results with experimental ones. Additionally, complexes were analyzed ADME properties to get insight into drug-likeness, and pharmacokinetic evaluation and the complexes were coherent with Veber and Egan rules.

Hawthorn vinegar is a fermented product with functional properties, containing phenolic compounds and bioactive ingredients that could promote health. In this study, ultrasound-ohmic (USOH) processing conditions were optimized using a hybrid machine-learning-based approach to maximize the α-glucosidase and α-amylase and inhibitory activities of hawthorn vinegar. A Box-Behnken experimental design with 27 runs was used, including four independent variables: ultrasound amplitude (40-80%), ultrasound duration (2-6 min), ohmic field strength (20-40 V/cm), and ohmic heating time (2-6 min). Thirteen machine learning algorithms were comparatively evaluated using systematic hyperparameter optimization with GridSearchCV and 5-fold cross-validation. The Lasso Poly2 model showed the highest predictive performance for both α-glucosidase and α-amylase inhibition, with CV R 2 values of 0.9301 and 0.9299, respectively, and low MAPE values (<1%). Metaheuristic optimization algorithms, including Particle Swarm Optimization (PSO), Differential Evolution (DE), and Gray Wolf Optimization (GWO), converged to similar optimum processing conditions, indicating the robustness of the optimized process region. Under the combined optimal conditions, the experimental α-amylase and α-glucosidase inhibition activities were 39.27 ± 1.36% and 37.54 ± 0.53%, respectively. In addition, USOH treatment significantly enhanced the phenolic profile of hawthorn vinegar compared to thermally pasteurized and untreated samples. In particular, the contents of chlorogenic acid, catechin hydrate, caffeic acid, rutin, naringin, resveratrol, and quercetin were markedly increased after treatment. Additionally, five phenolic compounds were evaluated by molecular docking analysis against α-amylase and α-glucosidase, and the strongest binding affinities were observed for naringin (-7.40 kcal/mol) and chlorogenic acid (-7.17 kcal/mol), respectively. These findings demonstrate that machine learning-assisted ultrasound-ohmic processing can effectively improve the antidiabetic and functional properties of hawthorn vinegar.

Mycophenolate mofetil (MMF) and its active metabolite, mycophenolic acid (MPA),are widely used immunosuppressive agents with emerging relevance in anticancer applications. In this work, their molecular characteristics were examined through a combined experimental and computational approach to better understand their physicochemical behavior and biological interaction profiles. UV–Vis absorption spectra recorded in DMSO, chloroform and ethanol showed excellent agreement with time-dependent DFT predictions, validating the reliability of the computational model. Geometry opitmization and electronic-structure analyses were performed using the B3LYP/SDD level of theory supported by ELF, LOL, and RDG topological descriptors to elucidate electron localization, delocalization, and non-covalent interactions. Frontier molecular orbital and global reactivity descriptors revealed distnict nucleophilic and electrophilic tendencies for MMF and MPA, respectively. Docking against key therapeutic targets VEGFR-2, ERK2, and TNFR1 demonstrated meaningful binding affinities through hydrogen bonding and hydrophobic interactions, with MPA showing relatively stronger interactions with VEGFR-2 and ERK2, while MMF displayed enhanced affinity for TNFR1. This study reveals how ligand coordination and metal identity systematically modulate the electronic structure of Au6, Ag6, and Cu6 clusters, with Cu6-based complexes showing the greatest reductions in the energy gaps and hardness, thereby enhancing their chemical reactivity. Overall, the combined spectroscopic, quantum-chemical, docking and molecular dynamics results provide a comprehensive moleculear-level understanding of MMF and MPA, supporting their continued exploration in immunosuppressive and anticancer drug development.

A series of benzimidazolium salts and their corresponding η⁶-arene–η¹-carbene ruthenium(II) complexes were synthesized and fully characterized. The well-defined half-sandwich Ru(II) complexes incorporate a strongly σ-donating benzimidazole-derived N-heterocyclic carbene ligand coordinated in an η¹-fashion, together with an η⁶-bound arene ligand, generating a robust piano-stool architecture. All compounds were characterized by 1H and 13C NMR spectroscopy, IR spectroscopy, and elemental analysis. The molecular structure of a representative complex was unambiguously confirmed by single-crystal X-ray diffraction analysis, verifying the η⁶-arene–η¹-carbene coordination mode and providing detailed insight into the metal coordination environment. The catalytic performance of the synthesized complexes was evaluated in the base-promoted transfer hydrogenation of various ketones using isopropanol as hydrogen donor and KOBut as base at 80 °C. Comparative catalytic studies indicate that the electronic and steric properties of the benzimidazole derived NHC ligands significantly influence catalytic efficiency within the η⁶-arene–η¹-carbene framework. The rigid benzimidazole backbone contributes to catalyst stability under basic conditions, while modulation of ligand substituents affects hydride formation and substrate coordination. These findings highlight the importance of rational ligand design in tuning the reactivity of η⁶-arene–η¹-carbene ruthenium(II) complexes for transfer hydrogenation applications. Additionally, the molecules were optimized using density functional theory (DFT) calculations, and the energies as well as spatial distributions of the frontier molecular orbitals were analyzed to gain insight into potential interaction residues.

AIMS:A synthesis of four silver(I) complexes was conducted, and they were evaluated for their antimicrobial properties and their ability to inhibit the formation of biofilms. Additionally, their binding affinities to DNA and BSA were investigated. MATERIALS & METHODS:The complexes, chloro[1-isopropyl-3-(3-methylbenzyl)-5,6-dimethylbenzimidazole-2-ylidene]silver(I) (2a), chloro[1-isopropyl-3-(3-chlorobenzyl)-5,6-dimethylbenzimidazole-2-ylidene]silver(I) (2b), chloro[1-methallyl-3-(3-methybenzyl)-5,6-dimethylbenzimidazole-2-ylidene]silver(I) (2c) and chloro[1-methallyl-3-(3-chlorobenzyl)-5,6-dimethylbenzimidazole-2-ylidene]silver(I) (2d) were prepared in 82-84% yields and fully characterized. The biological properties of both ligands and complexes were evaluated in vitro against S.aureus, E.faecalis, E.coli, A.baumannii, C.albicans, DNA and BSA. RESULTS AND CONCLUSIONS:The complexes 2a-d exhibited a significant inhibitory effect on diverse bacterial biofilms, with percentages ranging from 73.6% to 80.3% for S.aureus, 69.5% to 85.9% for E.faecalis, 76.9% to 88.6% for E.coli, 75.9% to 84.6% for A.baumannii and 70.1% to 82.3% for C.albicans. The most significant activities were observed with complex 2b at 8.5 µM. It was observed that silver(I) complexes exhibited more effective binding to DNA (4.92 × 103 for 2a), while NHC precursors displayed a higher binding affinity for BSA (5.52 × 104 with 1-isopropyl-3-(3-methylbenzyl)-5,6-dimethylbenzimidazole chloride). While the precursors of ligands exhibited significant toxicity at their highest MIC concentrations, the complexes demonstrated minimal toxicity.

AIMS:A synthesis of five palladium(II) complexes was conducted, and their binding affinities against deoxyribonucleic acid (DNA) and Bovine Serum Albumin (BSA) were evaluated. MATERIALS & METHODS:The PEPPSI-type complexes, dichloro[1-methallyl-3-(4-methylbenzyl)-5,6-dimethylbenzimidazolin-2-ylidene]pyridine palladium(II) (2a), dichloro[1-methallyl-3-(4-chlorobenzyl)-5,6-dimethylbenzimidazolin-2-ylidene]pyridine palladium(II) (2b), dichloro[1-methallyl-3-(4-tert-butylbenzyl)-5,6-dimethylbenzimidazolin-2-ylidene]pyridine palladium(II) (2c), dichloro[1-methallyl-3-(4-methoxybenzyl)-5,6-dimethylbenzimidazolin-2-ylidene]pyridine palladium(II) (2d) and dichloro[1-methallyl-3-(2,3,5,6-tetramethylbenzyl)-5,6-dimethylbenzimidazolin-2-ylidene]pyridine palladium(II) (2e), were synthetized in 74-82% yields. The structural characterization of the complexes was conducted through the utilization of 1H and 13C Nuclear magnetic resonance (NMR) spectroscopy, in conjunction with Fourier transform infrared (FT-IR) spectroscopy, mass spectroscopy and elemental analysis. DNA- and BSA-binding evaluation was performed spectroscopically with Benesi-Hildebrand Method and theoretically with molecular docking method. RESULTS AND CONCLUSIONS:According to the experimental method, complex 2a exhibited the strongest binding constant against DNA (1.84 × 104 M-1), while complex 2c demonstrated the highest BSA binding constant (2.83 × 104 M-1). Subsequent to molecular docking, and consistent with experimental findings, it was determined that all molecules exhibited interaction with the same DNA and BSA residues. Complex 2a demonstrated the strongest binding affinity against DNA, while complex 2c manifested the most robust interaction with a binding value of -8.09 kcal/mol. A thorough evaluation of the drug-likeness properties of the palladium(II) complexes was conducted using the SwissADME web tool.

Previously synthesized [MII(sac)2(aeppz)2] [M= Co (1), Ni (2), Cu (3), Zn (4), Cd (5); sac=saccharinate anion; aeppz=N-(2-aminoethyl)piperazine] type complexes which were structurally characterized have been further investigated electrochemically by cyclic voltammetry technique. Antioxidant activities of the complexes were evaluated using 1,1- Diphenyl-2-picrylhydrazyl (DPPH) and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals scavenging, Fe2+ chelating and superoxide dismutase activity methods and the results were compared with the uncoordinated aeppz ligand and the aeppz-free metal-saccharinate complexes. The molecules were also optimized using ORCA package program, molecular orbital diagrams were drawn, and highest occupied molecular orbital–lowest unoccupied molecular orbital (HOMO-LUMO) energy gap and electronic transitions of molecules were analyzed by Density Functional Theory (DFT)-Time Dependent DFT (TDDFT) calculations. Additionally, the reactivities of the molecules were evaluated for their Global Reactivity Descriptors according to Koopmans Theorem.

In an effort to promote eco-friendly organic synthesis, a facile, sustainable, and highly efficient procedure for the synthesis of 2-amino-1,3-thiazole derivatives was developed. The protocol of this process incorporates the principles of green chemistry. Moreover, the NMR, FT-IR, and UV simulations of the compounds were conducted at the B3LYP/6-311++G** level for comparison with the observed counterparts. FMO analyses revealed that the PhTA compound exhibited the highest stability via back-donation; among the compounds, NapTA exhibited the lowest stability via back-donation. Furthermore, the -NH2 group did not influence electrophilic attacks because the LUMO for all compounds did not separate from this group. Also, the lipophilicity, solubility, pharmacokinetics, and drug-likeness profiles of the compounds were evaluated. The BOILED-Egg model implied that the compounds PhTA, BFTA, and NapTA permeate through the BBB (blood-brain-barrier) passively, while the FTA and ThTA compounds have no potency in terms of BBB penetration. Also, all compounds met the requested physicochemical criteria according to the Lipinski, Veber, and Egan rules. Additionally, the molecules were analyzed using the molecular docking method to gain insights into their possible anticancer activity. Vascular endothelial growth factor receptor-2, human estrogen receptor, human cytochrome P450, and human extracellular signal-regulated kinase 2 were selected. All the obtained results are expected to provide important insights into the structure-reactivity relationship in early-stage drug design research.

BACKGROUND:Theophylline, which is biologically important and found in tea, coffee, and cocoa beans, can be synthesized chemically or by direct extraction and concentration from natural sources. Theophylline derivatives have garnered attention in recent years for their potential therapeutic effects on Mycobacterium tuberculosis, antihistaminic, anti-inflammatory, and anticancer. Also, trifluoromethyl (CF3) group has also been widely used in drug and agrochemical design. METHODS:In this study, a series of new theophylline derivatives containing substituted trifluoromethyl and trifluoromethoxy groups were synthesized. The structures of these new compounds were confirmed by NMR, FT-IR, and elemental analyses. Additionally, the anticancer activities of the molecules were analyzed against VEGFR-2, CYP P450, and estrogen receptor by molecular docking method. Furthermore, in vitro biological effects of the compounds were comprehensively evaluated in cancer (A549 and HeLa) and normal (BEAS-2B) cells. Cell viability was assessed by MTT assay, and selectivity index (SI) values were calculated to determine tumor-specific toxicity. RESULTS:N(7)-substituted theophyllines were prepared by the reaction of 1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (theophylline) and trifluoromethyl substituted benzyl halide compounds. The synthesized N(7)-substituted theophyllines were obtained as white powder in high yield. The structure of synthesized compounds was confirmed by various spectroscopic techniques such as 1H, 13C, 19F NMR, and FT-IR spectroscopy, and elemental analysis. The highest interaction was recorded as -5.69 kcal/mol for 3-CF3 substituted against VEGFR-2 structure while the best binding affinity was determined for 4-OCF3 substituted with -6.69 kcal/mol against Human Cytochrome P450 with in silico analysis. The in vitro anticancer activities of the molecules were also evaluated against A549 and HeLa cells, and displayed considerably higher cytotoxicity with 2-CF3, 3-CF3, and 4-CF3 substituted molecules in Hela and A549 cell line. To elucidate the molecular mechanism, apoptosis-related gene expression changes were analyzed by RT-qPCR in A549 and HeLa cells treated with compound 2-CF3. Significant upregulation of pro-apoptotic markers and downregulation of anti-apoptotic genes were observed. Consistently, ELISA-based quantification confirmed increased protein levels of Caspase-3, BAX, and Cytochrome C, and decreased BCL-2, validating the apoptotic mechanism at the protein level. Also, the antibacterial and antibiofilm activity details of the molecules were evaluated against DNA Gyrase, and SarA crystal structures by molecular docking method. The highest interaction was recorded as -5.56 kcal/mol for 2-CF3 substituted with H-bonds with Asn46, Val71, Asp73, and Thr165 against DNA Gyrase crystal structure while 3-CF3 substituted has the best binding affinity against SarA. The in vitro antimicrobial effects of the molecules were also evaluated. CONCLUSIONS:The synthesized molecules may provide insight into the development of potential therapeutic agents to the increasing antimicrobial resistance and biofilm-forming capacity of microorganisms. Additionally, compound 2-CF3 substituted exhibited promising and selective anticancer activity through apoptosis induction, supported by gene and protein level evidence.

Theophylline (1,3-dimethylxanthine) contains a fused imidazole-pyrimidine ring system with conjugated double bonds. It is a naturally occurring alkaloid that belonging to the xanthine family. Various substituted theophylline derivatives widely known as biologically active scaffolds. In this work, the N(7)-substituted theophylline compounds were synthesized and characterized by 13C-NMR, 1H NMR, elemental analysis, and FT-IR spectroscopy. The crystal structure of 1,3-dimethyl-7-[(3-methylphenyl)methyl]-2,3,6,7-tetrahydro-1H-purine-2,6-dione, 1b, was determined by single crystal X-ray diffraction analysis. The interactions of substituted theophylline type molecules with BSA were analyzed by the Stern-Volmer method and Stern-Volmer constants, rate constants, binding numbers, and binding constants of each molecule were determined. In addition, the interaction of BSA with the presence of Ca2+, Mg2+, and Zn2+ ions were investigated, and it was determined that the addition of metal ions decreased the binding values for all molecules except 1b. The details of the bindings detected for this study were also examined by the molecular docking method. The interactions of the N(7)-substituted theophylline compounds with DNA were analyzed by Benesi-Hildebrand method. The molecular docking method has also been used for the interactions of molecules against DNA.

N-(Benzo[d]thiazol-2-yl)benzamide and its derivatives are well known for their diverse pharmacological activities, including antimicrobial, anti-inflammatory, and anticancer properties, making their fusion a promising strategy for novel therapeutic agents. Our synthetic approach involved the condensation of 2-aminobenzothiazole with various substituted benzoyl chlorides. All synthesized compounds were fully characterized using spectroscopic techniques, including 1H NMR, 13C NMR, IR, and UV. Preliminary biological screening revealed that several derivatives exhibited a promising diverse range of pharmacological activities in the areas of life sciences and biology. Also, the recorded FT-IR, NMR, and UV-visible spectroscopic data of BA and chlorinated-BA isomers were compared with those of computational counterparts obtained from B3LYP/6-311G** level simulations. log P and log S simulations revealed that the BA compound would be more soluble in water and thus less lipophilic, whereas the chlorine-substituted isomers would be less soluble in water. Also, the iLOGP values of the compounds were calculated in the optimal range of -0.7 and +5.0, which indicated the potential for oral bioavailability. The BOILED-Egg model implied that BA and its isomers would have BBB penetration passively since all of them were located in the yolk region of the BOILED-Egg. FMO analyses implied that the BA compound would be less capable of charge transfer and gain more stability via back-donation, more than the chlorinated BA isomers. The characterized molecules were analyzed for BSA- and DNA-binding properties via UV-visible spectroscopy by the Benesi-Hildebrand method and fluorescence spectroscopy by the Stern-Volmer method. The best binding constants for both BSA and DNA binding were determined for 2CBA as 4.23 x 104 and 2.07 x 104, respectively. 4CBA has the best Stern-Volmer constants for BSA and DNA binding with values of 2.43 x 102 and 1.52 x 103, respectively. On the other hand, the highest binding number was determined for BA in BSA-binding experiments, while 4CBA has a binding number of 1.274 for DNA-binding evaluation. Additionally, BSA- and DNA-binding properties were also evaluated with molecular docking methods against BSA and DNA target crystals. According to both computational and experimental results, 2CBA has the best binding potential.

Designing CO-releasing molecules, which store, transport, and release carbon monoxide in the target tissue, has accelerated since scientists revealed that carbon monoxide is one of the transmitters and could be effective in treatment procedures. The most important candidates for this task are metal carbonyl complexes. In this study, [Mn-(CO)3(bpy)-L]-PF6-type metal carbonyl complexes were synthesized and characterized and the CO-releasing activities of these molecules were investigated. In addition, the optimization and theoretical analysis of the molecules were performed with DFT/TDDFT-based calculation methods. DFT computations at the B3LYP/6-311G-(d,p)/LANL2DZ level were performed to assign vibrational modes and NMR shifts following geometry optimization and confirmation. Moreover, NBO analyses were performed to predict the important electronic interaction that occurred in complexes: the results implied that the biggest contribution could come from the resonance interactions. FMOs analyses indicated that the 2e could be a softer (η= 1.511 eV) and is less stabilized complex via back-donation (Δεback‑donat. = -0.378 eV). Additionally, the interactions of the molecules with HSA, BSA, and DNA were investigated with molecular docking methods, and the binding properties of the manganese complexes were analyzed in vitro with UV-vis spectroscopy against BSA and DNA by the Benesi-Hildebrand method.

AIMS:Metal-N-heterocyclic carben (NHC) complexes have garnered significant attention from synthesis chemistry. Silver is well known for its broad-spectrum antimicrobial activity, and it exhibits their activities with different mechanisms. In this study, we combined these two important scaffolds, analyzed for possible antimicrobial and antibiofilm activity, and evaluated the interactions against DNA Gyrase, SarA, Human Serum Albumin, and DNA for getting insight into the antimicrobial and antibiofilm details. MATERIALS & METHODS:Four new Ag-NHC complexes (2a-d) were prepared from corresponding benzimidazolium salts (1a-d) and revealed by elemental analysis, FT-IR, NMR, LC-MS, and HRMS. The antimicrobial and antibiofilm properties of both ligands and complexes were evaluated with in-vitro and molecular docking methods which were performed against DNA Gyrase, SarA, Human Serum Albumin, and DNA. RESULTS AND CONCLUSIONS:1d showed superior activity while 2a and 2d were effective against C. albicans, with activity comparable to fluconazole in the range of 8.6-8.7 µM. The highest binding affinity was recorded for 2a as -7.93 kcal/mol against DNA Gyrase, while 2b has the best interactions with -5.49 kcal/mol against SarA. and -7.74 kcal/mol binding affinity was determined for 2a with molecular docking. All the molecules interacted with the same grove of DNA.