The phenyl-(2,6-di-2-pyrazinyl)pyridine derivatives (L1, L2) were synthesized using a one-pot Krohnke-type method, starting from 2-acetylpyrazine and substituted benzaldehydes. Their structures were characterized using a combination of spectroscopic (NMR, HRMS) and single-crystal X-ray diffraction techniques, complemented by density functional theory (DFT). Single-crystal X-ray diffraction reveals that L1 crystallizes in the C2/c space group (T = 296 K) with its supramolecular assembly being stabilized by C-H & ctdot;N and pi-pi stacking interactions, whereas L2 facilitates C-H & ctdot;N, N-H & ctdot;pi bifurcated, and pi-pi* interactions. The bio-interaction properties of L1 were studied using fluorescence spectroscopy with bovine serum albumin (BSA) as a model protein. Fluorescence studies demonstrated L1 induces static quenching of BSA, with a binding constant of 5.15 x 104 mol & sdot;dm-3. Synchronous and three-dimensional fluorescence spectra further demonstrated that L1 brings forth significant conformational changes in BSA. The compounds were evaluated for cytotoxicity against the HCT-116 human colorectal cancer cell line.

Hybridization of pharmacophores is a widely used strategy in anticancer drug design. Although lawsone and pyrazine scaffolds individually possess biological relevance, their combined hybrids remain comparatively less explored. A series of lawsone-pyrazine hybrids were synthesized through a Mannich-type reaction under sonication and evaluated against MCF-7 breast cancer cells. ADMET and drug-likeness properties were predicted using in silico tools. Cytotoxicity was assessed by MTT assay, followed by flow cytometric cell cycle analysis. Molecular docking, molecular dynamics simulations, and density functional theory (DFT) studies were also performed. Most compounds satisfied key drug-likeness criteria with minor deviations observed for L5. Compounds L7 and L8 showed notable antiproliferative activity with IC50 values of 6.75 +/- 0.75 and 5.22 +/- 1.82 & micro;M, respectively, comparable to standard drugs. Docking and MD studies suggested stable interactions of L7 with PR and L8 with HER2. Flow cytometry indicated G0/G1 phase arrest with increased sub-G0/G1 population, suggesting possible apoptotic involvement. Selected lawsone-pyrazine hybrids, particularly L7 and L8, demonstrated measurable antiproliferative activity supported by computational and cell-based studies, warranting further mechanistic investigation.

There is a strong demand for new and efficient antiviral compounds. A series of 2-hydroxy-1,4-naphthoquinone Mannich bases were screened for their HIV-1-RNase H inhibitory activity. An HIV-1-RNase H assay was used to study the RNase H inhibition by the test compounds. Docking of active derivatives into the active site of the enzyme was carried out. Compounds 1e and 2k showed distinctly higher HIV-1-RNase H inhibitory activity (IC50 = 2.8–3.1 µM) than the known inhibitors RDS1759 and compound 13. The binding mode and possible interactions of 1e and 2k with the HIV-1-RNase H active site were determined using molecular docking, which led to the identification of salient and concealed pharmacophoric features of these molecules. The docking analysis revealed that there are significant differences in the binding mode of these compounds within the active site of the target enzyme. A selection of HIV-1-RNase H-inhibitory Mannich bases was tested for antiviral activity against HIV-1, and compound 2k showed the highest activity at low toxicity to host cells. The lawsone Mannich bases 1e and 2k also underwent a preliminary screening for activity against SARS-CoV-2, and compound 1e was found to inhibit SARS-CoV-2 replication (IC50 = 11.2 µM).

A fluorescence chemosensor (E)-N'-(2-hydroxy-5-methoxybenzylidene) furan-2-carbohydrazide (L) comprised of 5-methoxy salicylaldehyde moiety has been synthesized and characterized employing 1 H NMR, 13 C NMR, FTIR and LCMS experiments. The chemosensor demonstrated remarkable selectivity towards Al3+ ion via 'turn-on' cyan colour fluorescence over Ni2+, Pb2+, Mn2+, K+, Na+, Hg2+, Co2+, Cu2+, Mg2+, Ba2+, Bi3+ and Fe3+ metal ions. A significant intensity enhancement (12-fold) for the wavelength maximum at 515 nm (lambda ex = 394 nm) against Al3+ ions was readily observed in aqueous medium until the saturation point has been reached. The limit of detection (LOD) for Al3+ was 82 nM, significantly lower than that threshold for Aluminium (7.4 mu M) in drinking water recommended by the World Health Organization. The stability constant was found to be 2.02 x 104 M-1 for the concentration up to 30 mu M. The detection potential for the receptor L was observed for pH ranging from 4 to 8. The 2:1 stoichiometry was suggested for the L-Al3+ complex from the Job's plot which was ascertained through Electrospray Ionization Mass spectrometry (ESI-MS) experiments. The sensing behaviour of L towards Al3+ is evidenced through 1 H NMR titration and infrared spectroscopy experiments in unison with Time-Dependent Density Functional Theory (TD-DFT).

Green synthesis is acknowledged as a crucial tool in mitigating the detrimental impacts linked to conventional methods of synthesizing organic compounds, which are commonly employed in both laboratory and industrial settings. In this study, a green chemistry approach was utilized for the synthesis of benzothiazol-2-yl(piperazin-1-yl)methanones scaffold, resulting in the synthesis of novel antimycobacterial chemotypes. A total of twelve benzothiazole-2-carboxamide compounds with distinct structural variations were successfully synthesized and subjected to in vitro testing against the Mycobacterium tuberculosis H37Rv strain to evaluate their potential as anti-tubercular agents. All the synthesized compounds were analyzed by FTIR, NMR, and Mass spectral analysis. Structures of 5a, 5g, and 5l were confirmed by single crystal X-ray diffraction. All synthesized compounds displayed potential anti-mycobacterial activity with MICs in the low range. The synthesized compounds were also subjected to evaluation of binding interactions with target protein, and molecular dynamics simulation. The compounds 5a, 5f, 5g, 5h, and 5l have shown significant docking scores i.e., -8.0, -8.9, -9.1, -8.9, -8.8 kcal/mol respectively to interact with tuberculosis protein followed by other compounds with the related targets of DprE1, Polyketide synthase, and Protein kinase B. Thus, the substantial anti-TB of benzothiazole-2-carboxamides (5a-l) derivatives implies that; these scaffolds could help in assisting the development of lead compounds for the treatment of antitubercular infections.

Hexavalent chromium (Cr (VI)) contamination in water sources poses severe environmental and health risks due to its carcinogenic nature. Recent advances in nanotechnology have reported promising solutions for remediating Cr (VI)-contaminated environments. Compared to bulk zero-valent iron, nano-nickel exhibits superior electrical conductivity and facilitates faster electron transfer during redox reactions, thereby enhancing Cr (VI) reduction efficiency. Unlike zero-valent iron, which oxidizes readily, nano-nickel is more resistant to corrosion, offering greater stability in aqueous environments and extending its functional lifespan. This study investigates the efficacy of green-synthesized nickel nanoparticles (Ni NPs) for reducing Cr (VI) to the less toxic trivalent chromium (Cr (III)). Ni NPs were synthesized using an eco-friendly approach with Ocimum sanctum (Tulsi) seed extracts serving as both reducing and stabilizing agents. The synthesized Ni NPs were characterized using FE-SEM, TEM, EDS with elemental mapping, XRD, XPS, and FTIR techniques. Batch experiments were conducted to assess Cr (VI) reduction under varying conditions, including Ni NP dosage, initial Cr (VI) concentration, pH, and contact time. Results showed efficient Cr (VI) reduction, with a significant decrease in Cr (VI) concentration within 20 min. The effect of pH was also studied, revealing an optimal reduction at pH 2. Kinetic analyses further elucidated the reduction mechanism, showing that the reaction follows first-order kinetics with a high linear regression coefficient (R2 = 0.9764–0.9923) across tested concentrations. These findings demonstrate that green-synthesized Ni NPs provide an efficient, eco-friendly, and cost-effective strategy for Cr(VI) remediation, supporting sustainable approaches for environmental protection and public health.

In the current study, four new 3-acetyl-6-bromocoumarin hydrazones (3a-3d) were synthesized, and their structures were characterized using FTIR, 1H-NMR, and HRMS techniques. The antioxidant activity of these hydrazones was evaluated using the DPPH radical scavenging method. Among them, hydrazones 3c and 3d exhibited significant antioxidant activity, with noteworthy IC50 values compared to the standard antioxidant, ascorbic acid. These results may be attributed to the presence of various functional groups, which could have enhanced the activity of 3c and 3d. Overall, the findings suggest that these compounds could serve as promising lead structures for the development of new drugs.

This study outlines the synthesis of pyrazine sulfonamides (3 a-3 i) along with halo-phenyl derivatives (4 a-4 j and 5 a-5 e). The antiproliferative effects were tested against MCF-7 breast cancer, and colon carcinoma HT-29, HCT-116 WT, and HCT-116 p53 knock-out mutant cell lines. Compounds 3 b and 3 c were notably active against HCT-116 WT cells, while 3 e and 3 h were moderately effective against MCF-7 cells. Among the halo-phenyl sulfonamides, 4e and 4j were active against MCF-7 cells, and 5 b was active against HCT-116 WT cells. The most promising compounds were evaluated against non-tumorigenic cells, demonstrating cancer selectivity. Compounds 3 b, 3 c, 3 e, 3 h, and 5 b showed dose-dependent inhibition of colony formation. Compound 3 f exhibited free radical scavenging activity comparable to ascorbic acid. Molecular docking revealed strong binding to thymidylate synthase (3 b, 5 b), Akt-3 protein kinase (3 e, 3 h, 4 e, 4 j), and tyrosinase (3 f, 3 h). The compounds also exhibited antiparasitic activity against Toxoplasma gondii and Leishmania major, with modifications enhancing selectivity for T. gondii. Substitutions in compounds 4 b and 4 d increased activity against T. gondii while reducing toxicity. Notably, compound 4 f emerged as a T. gondii-selective lead drug. These findings suggest sulfonamides may help treat complex diseases like cancer and infections.

We report the synthesis, structural characterization and antioxidant activity of biologically active hydrazonesQ-1 to Q-5 from2,6-di-tert-butyl-1,4-benzoquinone and hetero aromatic hydrazides. The hydrazone, Q-2 shows a notable antioxidant potential of 9.09 +/- 0.48 mu g/ml as compared to ascorbic acid. All the derivatives were screened virtually for ADMET, physicochemical properties, drug likeness and molecular docking studies. These hydrazones showed good pharmacodynamics and physicochemical properties, as well as no violations in drug-likeness predictions. These compounds were further subjected for possible target prediction and the compounds were found to target enzymes in the biological systems. Further, these compounds were docked in COX-2 (PDB Id: 6COX) protein and found to exhibit reasonably good interactions with amino acid residues, showed a good binding energy and fit favorably into the 6COX active site displaying hydrogen bonding with different amino acid residues of the target protein. The experimental results of the antioxidant activity fit well with the predicted in silico results. Therefore, these new derivatives (Q-1 to Q-5), containing a quinone and an azomethine group, can become good drug candidate for designing new drug and can be considered for further optimization and lead development.

Pomegranate fruit is a boon for humankind as it has the ability to promote human health due to its antioxidant, anti-inflammatory, antitumoural and antidiabetic activities.Cauliflower leaves are rich source of carotene, iron and calcium but it has higher waste index.However, cauliflower leaves assist in overcoming the health related problems and prevent anemia.The present study provides more evidence on the importance and value of pomegranate fruit, especially pomegranate's mesocarp and cauliflower leaves which are usually considered as a waste product.According to the phytochemical screening, pomegranate mesocarp contains tannins, flavonoids, terpenoids and alkaloids and cauliflower leaves contain alkaloid, terpenoid, sterols, flavonoid and vitamin C. The amounts of extractable components using different solvents (methanol, water, petroleum ether, and chloroform) from pomegranate mesocarp and cauliflower leaves ranged from 0.57-0.02mg/100 ml and 0.3-0.02mg/100 ml, respectively.In both methanol and water extract tannin was highly found in methanol extract of pomegranate mesocarp, i.e., 0.35 mg/100 ml.Concentration of flavonoids in pomegranate mesocarp ranged from 0.24 mg/100 ml to 0.02 mg/100 ml, i.e., highest in methanol and water extract, respectively, and lowest in pet ether extract.Concentration of flavonoid in cauliflower leaves was found in methanol extract, i.e., 0.08 mg/100 ml.Concentration of protein in pomegranate mesocarp ranged from 0.42 mg/100 ml to 0.02 mg/100 ml, i.e., highest in methanol extract and lowest in chloroform extract.Concentration of protein in cauliflower leaves ranged from 0.3 mg/100 ml to 0.04 mg/100 ml.Phenolic content in pomegranate mesocarp ranged from 0.57 mg/100 ml to 0.03 mg/100 ml, i.e., highest in water extract and lowest in chloroform.Phenolic content in cauliflower leaves ranged from 0.15 mg/100 ml to 0.03 mg/100 ml, i.e., highest in pet ether and lowest in chloroform and water, respectively.Concentration of antioxidant activity in pomegranate mesocarp ranged from 0.28 mg/100 ml to 0.03 mg/100 ml, i.e., highest in methanol and lowest in chloroform as well as pet ether.Concentration of antioxidant activity in cauliflower leaves ranged from 0.22 mg/100 ml to 0.02 mg/100 ml, i.e., highest in methanol extract and lowest in chloroform extract.The quantitative assays showed that the total content of phenolic compounds flavonoids, concentration of proteins and antioxidant activity in pomegranate mesocarp was higher than that of cauliflower leaves.

Green protocol of synthesizing nanoparticles has emerged as an optional way to overcome the limitation of the conventional physical and chemical methods. In the present paper, we wish to report a green synthesis of iron nanoparticles employing the aqueous root extract of Picrorhiza kurroa plant as an effective reducing and stabilizing agent. The green nanoparticles thus prepared are characterised using UV–Visible, FTIR, XRD and FESEM techniques. The average particle size of biosynthesised iron nanoparticles was found to be 26 nm. The antioxidant activity of these nanoparticles was determined by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical method. It was found to have IC50 value comparable with that of standard ascorbic acid. The in-vitro antibacterial activity of biosynthesised iron nanoparticles was evaluated using an agar disc-diffusion method against Gram positive and Gram negative bacteria and has displayed their potential efficacy.

In this work, the multifunctional potential of four 3-acetylcoumarin derivatives was studied. The derivatives were significantly active against bacteria Staphylococcus aureus, Pseudomonas aeoginosa and fungal strain Candida albicans. The results of antioxidant activity assays were promising when compared to ascorbic acid. The in vitro anticancer activity was carried out using MTT assay on human cancer cell line COLO-205 and 3ACDT showed commendable antiproliferative activity along with appreciable tumor selectivity with distinct selectivity index. Moreover, ADMET properties of the compounds were determined using the pKCSM and SwissADME online tools and all compounds were found with good pharmacokinetic profile. Hence, from the obtained results from all the 3-acetylcoumarin derivatives, 3ACDT exhibited good therapeutical potential and can be optimized for lead development.

We report the synthesis, structural characterization and pharmaceutical activity of four coumarin-quinone hybrids. The compounds were significantly active against Staphylococcus aureus, Pseudomonas aeoginosa and Candida albicans. Promising antioxidant activity was observed when compared to ascorbic acid. Two compounds, DTBSB and DTBSN, also showed commendable in vitro antiproliferative activities against the cells of human cancer cell lines MCF-7, MDA-MB-231, COLO-205, HT-29 and A549 along with appreciable tumor selectivity with distinct selectivity index. Molecular docking studies using cyclooxygenase-2 (PDB ID: 6COX) revealed strong binding affinities for the COX-2 active site. Moreover, ADMET properties of the synthesized compounds were determined using the pKCSM and SwissADME online tools and all the compounds had accurate pharmacokinetic profiles. Hence, the new coumarin-quinone hybrids DTBSB and DTBSN can be considered for optimization and lead development.

We report the synthesis, spectroscopic characterization, molecular docking and biological evaluation of nine pyrazino-imidazolinone derivatives. These derivatives were evaluated for their anticancer activity against three cancer cell lines: 518A2 melanoma, HCT-116, and HCT-116 p53 knockout mutant colon carcinoma. The MTT assay was employed to assess their effectiveness. Among the nine compounds tested, four compounds (5 a, 5 d, 5 g, and 5 h) exhibited promising antiproliferative activity specifically against HCT-116 p53-negative cells (IC50 0.23, 0.20, 2.07 and 58.75 μM, respectively). Interestingly, treatment with the 3,4-dimethoxyphenyl derivative 5a resulted in a significant increase (199 %) in caspase activity in HCT-116 p53-negative cells compared to untreated cells while the bromo-pyrazine derivative 5d demonstrated (190 %) increase. These findings suggest that compounds 5a and 5 d induce p53-independent apoptotic cell death. Additionally, in silico molecular docking studies with EGFR and tyrosinase proteins indicated that compounds 5 d and 5 e have the potential to bind to important anticancer drug targets.

A series of curcumin-pyrimidine analogs (3a-3h) were synthesized with good yields using phase transfer catalysis. The antiproliferative activities of the synthesized compounds were examined against two human breast cancer cell lines, MCF-7 and MDA-MB-231. Compounds 3b and 3g demonstrated potent antiproliferative activity against MCF-7 cancer cell lines with an IC50 value of 4.95 ± 0.94 µM and 0.61 ± 0.05 µM respectively. Compounds 3b and 3g displayed significantly less cytotoxicity towards non-tumorigenic MCF-10A cells. Further, 3b and 3g were investigated for cell cycle analysis and colony formation assays. Flow cytometry showed cell cycle arrest and induced apoptosis in dose and time-dependent manner. In colony formation assay, 3b and 3g caused a significant decrease in the number of colonies in MCF-7 cell line. Molecular docking studies against human epidermal growth factor receptor 2 (HER2) (PDB ID:3PP0), estrogen receptor (PDB ID: 3ERT), and progesterone receptor (PDB ID: 3G8O) showed strong binding interactions. Curcumin-pyrimidine analogs are synthesized and screened against MCF-7 and MDA-MB-231 cancer cell lines. Two analogs showed higher in vitro antiproliferative activities against MCF-7 with IC50 values of 4.95 and 0.61 µM. These compounds induce apoptosis in cycle analyses, inhibit colony formation, and show good binding interactions in molecular docking studies.

Based on the promising c-Myb inhibitor 1b, a series of 2-amino-4-aryl-4H-naphtho[1,2-b]pyran-3-carbonitriles (1a, 2a-q, 3a-g) were repurposed or newly synthesized via a three-component reaction of 1-naphthol, and various aryl aldehydes and malononitrile and screened for their c-Myb inhibitory activities. 1b also served as a lead compound for seven new naphthopyran derivatives (3a-f), which were cytotoxic with nanomolar IC50 values, to inhibit the polymerization of tubulin, and to destabilize microtubules in living cells. Especially, the alkyne 3f, originally made for intracellular localization studies using click chemistry, showed an overall high activity in all assays performed. A strong G2/M cell cycle arrest was detected, which resulted in a distinct increase in sub-G1 cells through the induction of effector caspases 3 and 7. Inhibition of angiogenesis was confirmed in vitro and in vivo. In summary, 3f was found to be a pleiotropic compound with high selectivity for cancer cells, combining c-Myb inhibitory, microtubule destabilizing, and antiangiogenic effects.

Pyrazines are important class of pharmacophores because of their versatility in pharmacological activity. Pyrazines are among the most widely known heterocyclic compounds those can be isolated from natural sources or produced synthetically. Many substituted pyrazines are produced naturally and are widely distributed in plants, animals, including marine organisms. These heterocyclic analogs have been proven important scaffold in perfumeries, food industries and pharmaceuticals. Due to diverse biological activities of pyrazine-based drugs, a rise in investigations of pyrazine containing candidates has been observed. In recent past numerous advancement has been taken place to explore their synthetic pathways and biological activities. This review focuses on biosynthesis of different pyrazine derivatives and their various biological activities.

Under solvent free conditions and in presence of a base 3-(2-(subsituted-(trifluoromethyl)phenylamino)acetyl)-2H-chromen-2-one derivatives were synthesized by grinding technique. Structural investigations were carried out with IR studies, HRMS, 1HNMR and 13CNMR. The compounds were checked for their in vitro anticancer activities against three different human cancer cell lines viz human breast cancer cell line (MCF-7), human cervical cancer cell line (HeLa) and human oral squamous cell carcinoma (SCC-40) using SRB method. All the title compounds showed low toxicity towards non-malignant PBMC cells indicating their tumour selectivity. The compounds exhibited good in vitro anti-proliferative potency at lower concentrations against HeLa and MCF-7 cell lines and remain moderately active against SCC-40.