In the present context to rationalize the search for new effective antimicrobial agents against the infections caused by microbes, a series of benzoxazine/benzothiazine appended 1,2,3-triazole hybrids were designed and synthesized via click reaction with ingredients of two or more bioactive moieties through the concept of molecular hybridization. Various spectral techniques such as FTIR, H-1 NMR, C-13 NMR, 2D NMR and HRMS were utilized for structural elucidation of the synthesized hybrids. The serial dilution method was employed for performing the antimicrobial activity of synthesized triazoles against four bacterial (S. aureus, B. subtilis, E. coli, K. pneumoniae) and two fungal (C. albicans, A. niger) strains. The antibacterial results demonstrated that a couple of hybrids show noteworthy outcomes related to standard medication. Compound 4r was indicated great action against E. coli with MIC values 0.0259 mu mol/mL. Based on outcomes of antibacterial activity, molecular docking study was carried out with E. coli DNA gyrase to understand the binding behavior. To check out the drug-likeness, in silico ADME (Absorption, Distribution, Metabolism and Excretion) studies of synthesized hybrids were also analyzed and found that compounds can be developed as potential oral drug candidates.

A library of thiazole/benzothiazole linked 1,4-disubstituted 1,2,3-triazoles having ester-amide functionality was synthesized in good yields through Cu(I)-promoted click reaction between prop-2-yn-1-yl benzoates / prop-2-yn1-yl naphthoates and 2-bromo-N-(thiazol-2-yl)acetamide/ N-(benzo[d]thiazol-2-yl)-2-bromoacetamide and sodium azide. Different analytical techniques like FTIR, 1H NMR,13C NMR and HRMS were used for characterization of the synthesized 1,2,3 triazoles. The synthesized molecules were also screened for in vitro antimicrobial activity against S. aureus, B. subtilis, E. coli, K. pneumoniae, C. albicans, A. niger as well as antioxidant activity. Amongst the synthesized triazoles, compound 7l (1-(2-(benzo[d]thiazol-2-ylamino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methyl 4-bromobenzoate and compound 7n (1-(2-(benzo[d]thiazol-2-ylamino)-2-oxoethyl)-1H-1,2,3triazol-4-yl)methyl 4-nitrobenzoate displayed excellent activity against all the tested bacterial and fungal strains. Further, compound 7f and 7n exhibited good antioxidant activity. ADME analysis and molecular docking studies against DNA gyrase (S. aureus) were also performed to get an insight into the drug-likeliness properties and mode of action.

Osteoarticular tuberculosis (OATB) remains a significant global health challenge with high morbidity and potential for permanent disability. Recent advancements in diagnostics, pharmacotherapy, and adjunctive treatments have shown promise for improving the outcomes of patients with OATB. This review summarizes the latest developments in the field, focusing on epidemiology, pathogenesis, diagnostic innovations, novel anti-tuberculosis drugs, combination therapy approaches, surgical interventions, adjunctive therapies, and the importance of multidisciplinary approaches. Emerging diagnostic technologies such as advanced imaging modalities, molecular assays, and nanotechnology-based tests have enhanced the speed and accuracy of OATB detection. Newer anti-tuberculosis drugs, including bedaquiline, delamanid, and pretomanid, have demonstrated efficacy in multidrug-resistant (MDR) and extensively drug-resistant (XDR) cases, whereas DprE1 inhibitors and oxazolidinone alternatives show promise in early phase trials. Minimally invasive surgical techniques, joint-preserving procedures, and reconstructive methods using 3D-printed implants and antibiotic-loaded materials have improved functional outcomes. Immunomodulators, bone grafts, and regenerative medicine have been explored as adjunctive therapies. Effective management of OATB requires collaboration among various specialists, and integrated care models facilitate personalized treatment plans. Challenges remain, including drug resistance, and the need for further research to establish optimal regimens and durations specific to OATB. By highlighting key advancements and their potential impact on patient outcomes, this review underscores the importance of a multidisciplinary evolving paradigm for treating OATB in the era of precision medicine.

Background: Osteoarticular tuberculosis (OATB) is a challenging form of extrapulmonary tuberculosis (TB) that often requires long-term multidrug regimens. Antitubercular therapy (ATT) can lead to significant adverse drug reactions (ADRs), potentially affecting patient adherence and outcomes. Objectives were to assess the types and frequencies of ATT-induced ADRs in patients treated for osteoarticular TB. Methods: This retrospective observational study included 27 patients diagnosed with OATB, who were treated at Dr. RPGMC Tanda. Patient records and telephone interviews were used to collect data on ADRs. Descriptive statistics were used for analyses. Results: Of 27 patients, 13 (48.1 %) experienced ADRs. GI symptoms were the most common (18.5%), followed by dermatological (11.1%) and neurological (11.1%) side effects. One case each of hepatotoxicity with liver failure and epistaxis, and two cases of ocular symptoms were recorded. Conclusions: Nearly half of the patients developed ADRs to ATT. Regular monitoring and early intervention are essential to improve treatment compliance and patient safety.

The fastest growing class of materials in chemistry is that of the metal organic frameworks (MOF's), consisting of metal nodes and organic linkers as building units. There exist numerous inorganic ligands to coordinate with metal ions but certainly various organic linkers are also available. Amongst the broadly available heterocyclic compounds, pyrazole functionalities have achieved greater attention owing to their wide-ranging applications. Recently, applications of pyrazole ligands in coordination compounds and structured porous materials such as metal organic frameworks have undoubtedly created considerable interest in developing newer frameworks. Utility of these hybrid compounds in adsorption, fluorescent and colorimetric analysis, drug delivery, catalysis and sensing/detection of analyte are receiving significant interest. Reference to the enormous background on the synthesis and biological resourcefulness of pyrazoles, this review proposes a brief survey on applications of pyrazole ligands in coordination compounds and metal organic frameworks.

Background: Azole and sulfonamide molecular frameworks are endowed with potent antimicrobial activity. Materials & methods: A series of azole–sulfonamide conjugates were synthesized using click reaction of N-propargylated imidazole with azide of sulfonamide and its antimicrobial efficacy was evaluated. Results: The compounds 7c, 7i and 7r displayed promising antibacterial activities, better than the standards sulfonamide and norfloxacin. All molecules exhibited promising antifungal activity, more potent than fluconazole. Docking studies of the active conjugates signified the importance of hydrophobic interactions in hosting the molecules in the active site of dihydrofolate reductase. Conclusion: Azole–sulfonamide conjugates are more active than single sulfonamide moieties and 7c, 7i and 7r may prove valuable leads for further optimization as novel antimicrobial agents.

Background Sulfonamide, imidazole, and triazole chemical nuclei possess good antimicrobial potential.Aims This study aimed to amalgamate sulfonamide, imidazole, and triazole moieties in a single molecular framework with the intent of improving their antimicrobial activities.Objective The objective of this study was the synthesis of conjugates containing sulfonamide and azole moieties along with in vitro and in silico evaluation as antimicrobial candidates.Method A series of sulfonamide-modified azoles (7a-r) was synthesized by multicomponent condensation of 1,2-dicarbonyl compounds, ammonium acetate and aryl-substituted aldehydes in glacial acetic acid. The structure of synthesized molecules was elucidated with the help of various spectroscopic techniques, such as FTIR, NMR, and HRMS. The target molecules were tested for in vitro antimicrobial potency against four bacterial strains and two fungal strains.Result Molecules 7c (MIC 0.0188 mu mol/mL), 7f (MIC 0.0170 mu mol/mL) and 7i (MIC 0.0181 mu mol/mL) were most active against S. aureus and C. albicans. Against E. coli, molecules 7d (MIC 0.0179 mu mol/mL), 7f (MIC 0.0170 mu mol/mL) and 7i (MIC 0.0181 mu mol/mL) were found to be highly active. Moreover, the binding conformations were investigated by in-silico molecular docking, and QTAIM (Quantitative theory of atoms in the molecule) analysis was also performed. Molecular properties, such as the heat of formation, HOMO energy, LUMO energy and COSMO volume, were found to be in direct correlation with the antimicrobial potency of molecules 7c, 7f and 7i against S. aureus and C. albicans.Conclusion All the synthesized molecules were more potent than clinically approved sulfonamides, namely sulfadiazine and sulfabenzamide.

Synthesis of phenyl/benzothiazole functionalized C-C linked pyrazolyl-thiazoles has been achieved from non-lachrymatory alpha-tosyloxy pyrazolylketones with different thioamides. The pyrazolyl-thiazoles were characterized by spectroscopic studies and evaluated for antimicrobial activity and phytotoxicity. Compound 6 n displayed better activity with MIC value of 0.0045 mu mol/mL against Gram-positive bacteria B. cereus in comparison to the standard drug Ciprofloxacin (0.0047 mu mol/mL). Compound 6 i displayed better activity against fungal strain C. albicans (MIC=0.0152 mu mol/mL) in comparison to the standard drug Fluconazole (0.0204 mu mol/mL). Compound 6 o diplayed 95 % cell viability against Mouse Fibroblast cell line and 100 % plant seed germination. Docking studies at the topoisomerase II DNA gyrase B (PDB ID: 1KZN) and C. albicans (PDB ID: 1IYL) were used to investigate potential interactions between the most active compound and the receptor protein. The stability of the compounds with 1KZN and 1IYL by molecular dynamic simulations showed that 6 r, 6 n and 6 i present leading structures for next drug development because of their simple synthesis and useful bioactivity.

Utility of pyrazoles and their derivatives in constructing ordered porous materials with physicochemical characteristics such as chemosensors has undoubtedly created much interest in developing newer frameworks. A variety of pyrazole based chemosensors are known for their remarkable photophysical, pH sensitivity, solvatochromic, ion detection, high quantum yields and nonlinear optical behavior. Many of the transition metals have shown beneficial biological effects in biological systems. There is always a need of continuous monitoring to maintain an adequate range of all and specifically for the toxic ones like mercury. Pyrazoline nanoparticle probes have been reported for sensing/detection of Hg2+ions. Pyridinyl pyrazoline and benzimidazolyl pyrazole derived sensors are more selective and sensitive towards Zn2+and Fe3+ ions respectively. Pyrazole derived metal organic frameworks (MOF's) have been reported for environmental monitoring and biological imaging. Keeping in view of the enormous synthetic and biological importance of pyrazoles, herein, we are presenting an overview on applications of pyrazoles in transition metal chemosensors.

A series of 1,4-disubstituted 1,2,3-triazoles with amide-hydroxyl functionality (5a–5t) was synthesized from aliphatic alkynes (4a–4e) and aromatic bromides (3a–3d) in presence of catalytic amount of cellulose CuI nanoparticles. All the synthesized triazoles were characterized by various analytical techniques: FTIR, 1 H NMR, 13 C NMR and HRMS. Further, all the synthesized compounds were screened for in vitro antioxidant and antimicrobial activities. The antioxidant activity of the compound 5s was found better than other compounds. Compounds 5h and 5l exhibited good antibacterial and antifungal activity, respectively. The docking studies were performed to find out various binding interactions of protein-ligand complex. In silico ADME study was performed to evaluate their drug likeness.

Synthesis of a number of highly oxygenated furo[3,2-c]pyran/chromen-4-one has been accomplished by one-pot reaction from easily available dehydroacetic acid/3-acetyl-4-hydroxycoumarin or their chalcones and alpha-bromoketones. All the synthesized molecules were characterized utilizing various spectroscopic techniques and screened for anticancer activity (in vitro) against three colon (HCT-116, SW-620, HT-24), lung (A-549), prostate-(PC-3), breast (MCF-7) cell lines. Compounds 5a, 9d, 9f showed good activity against breast MCF-7 cancer cell line having IC50 values 6.9, 2.8, 5.3 mu M, respectively. Of these compounds, 9d showed better activity against prostate PC-3 cell line with IC50 value 3.8 mu M. The synthesized compounds were also studied for antibacterial activity (in vitro) using different strains of bacteria (Bacillus subtilis and Staphylococcus aureus - Gram-positive and Escherichia coli, Pseudomonas aeruginosa - Gram negative) as well as fungal strains (Aspergillus niger and Candida albicans) using Norfloxacin and Fluconazole as antibacterial and antifungal standard drugs, respectively. The antimicrobial screening study showed that compound 9f exhibited promising activity against S. aureus and B. subtilis, while 5h showed excellent and 5i and 9b showed better activity against E. coli. Compounds 5d and 5e showed promising activity against P. aeruginosa. The compounds 5c-5e displayed excellent activity against C. albicans and A. niger than Fluconazole.

A series of twenty 2-(2-((1-aryl-1H-1,2,3-triazol-4-yl)methoxy)phenyl) benzoxazoles were synthesized from different aryl azides by copper catalyzed [3+2] cycloaddition reaction in 78-88 % yield. The structure of products was elucidated using spectroscopic techniques. These compounds were tested for cytotoxicity against five cancer cell lines [MCF-7 (Breast), HT-29 (Colon), Hep-G2 (Liver), A549 (Lung) and PC-3 (Prostate)] using the standard drug Adriamycin. It was found that 2-(2-((1-(3,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzoxazole (6 g) was active against all the above cancer cell lines with good activity against PC-3 cancer cell line (GI(50) value 60 mu M) comparative to Adriamycin (GI(50) value 0.3 mu M). Compound 6 g also displayed significant antioxidant activity (IC50 value 4.56 mu M) as compared to standard ascorbic acid (IC50 value 9.10 mu M).

Phenyliodine(III) diacetate-induced oxidation of 2-(2-hydroxynaphthyl)benzoxazoles in alcohols, regioselectively afforded dearomatized products: 1-(benzoxazol-2-yl)-1-alkoxynaphthalen-2(1H)-ones and 1-(benzoxazol-2-yl)naphthalene-2,3-diones. Further, these products were also synthesized in one-pot either from (E)-1-(((2-hydroxyphenyl) imino)methyl)naphthalen-2-ol or 2-aminophenol and 2-hydroxynaphthaldehyde by varying the amount of phenyliodine(III) diacetate in different alcohols. The structure of these compounds was established on the basis of FTIR, NMR, and mass spectral data as well as X-ray crystallographic data.

2,4,5-Triaryl-1H-imidazole hybrids were synthesized from substituted benzil and indole-3-aldehyde which on subsequent treatment with aryl azides converted to 1,2,3-triazoles by employing click chemistry. All the synthesized hybrids were characterized by FTIR, H-1-NMR, C-13-NMR spectroscopy and HRMS. These scaffolds were tested in vitro for their antifungal evaluation against different candida species. Screening against the used fungal strains, the results outcome that imidazole-indole hybrids bearing antifungals more effectively reduced than imidazole-indole-1,2,3-triazole hybrids with their MIC80 values in the range of 2-128 mu g/mL. Among all the synthesized hybrids, 2a and 2b were found to be the most potent against fungal strains as a result of different methods like, time kill assays, effect on fungal membrane and antibiofilm activity. The docking simulations of the most active hybrids, 2a, 2b and 2c were carried out in the active site of sterol 14-alpha demethylase enzyme of Candida albicans.

In the current research work, a new series of benzimidazole-1,2,3-triazole-indoline derivatives (5a–r) were designed and synthesized by employing click reaction between substituted N-propargylated benzimidazole derivatives and in situ formed substituted 2-azido-1-(indolin-1-yl)ethanone derivatives in moderate to good yields. The structure of the prepared compounds was confirmed with the help of 1D, 2D-NMR, FTIR and HRMS. The synthesized compounds have been evaluated for their biocidal effects against four bacterial and two fungal strains. The obtained results indicate stronger inhibitory effect of compound 5o against E. coli, while compound 5r showed good inhibition against all the tested strains except B. subtilis. In vitro α-glucosidase inhibition of all synthesized derivatives identified 5p (IC50 value = 0.015 ± 0.0003 μmol/mL) and 5r (IC50 value = 0.018 ± 0.0008 μmol/mL) as potent inhibitors of α-glucosidase, even better than standard drug Acarbose. Molecular modelling studies into the binding sites of α-glucosidase indicate the stable anchoring of 5p and 5r with favourable binding interactions. In addition, pharmacokinetic/dynamic attributes of compounds were estimated by using the ADMET profile.

A small library of novel pyrazolyl-imidazole-triazole hybrids ( 3a-3r ) has been designed and synthesized based on hybrid pharmacophore approach using click reaction of N-propargylated pyrazolyl-imidazole ( 1 ) with several aryl azides carrying different substituents. The hybrids were characterized by different spectral techniques like IR, H-1, C-13 NMR, HRMS and X-ray crystallography. ADME profile was assessed for these derivatives to get an insight on their pharmacokinetic/dynamic attributes. The synthesized hybrids were screened for antimicrobial activities against bacterial and fungal strains. Hybrid 3o and 3k demonstrated broad spectrum antibacterial activity against all tested bacterial strains except S. aureus and even better than clinically approved drug Norfloxacin. Hybrids 3c (MIC, 0.0082 mu mol/mL), 3d (MIC, 0.0075 mu mol/mL), 3e (MIC, 0.0077 mu mol/mL) and 3m (MIC, 0.0081 mu mol/mL) showed more than two-fold inhibitory efficacy against C. albicans while against A. niger, 3c (MIC, 0.0082 mu mol/mL) showed five-fold inhibitory efficacy as compared with Fluconazole. Moreover, in-silico molecular docking study investigated on E. coli topoisomerase-II DNA gyrase revealed a good binding interaction with most potent hybrids 3o and 3k . (C) 2022 Published by Elsevier B.V.

Sixteen new benzimidazole hybrids containing 1,2,3-triazole and piperazine scaffolds have been synthesized by click reaction. The synthesized hybrids were characterized by various spectroscopic techniques like IR, NMR and HRMS, and further examined in-vitro for their α-amylase and α-glucosidase inhibitory potential. The hybrid 5p was active against α-amylase with IC50 value of 0.0327 µmol/mL and hybrids 5h, 5o and 5p were active against α-glucosidase with IC50 values of 0.0154, 0.0156 and 0.0144 µmol/mL, respectively, comparable to acarbose. Docking analysis of α-glucosidase with 5o and 5p showed effective binding to hydrophobic cavity and form hydrogen bonding with the His348 and Arg439 residues. DFT and molecular electrostatic potential studies supported in-silico and in-vitro biological screening results. The pharmacological profile revealed that 5o and 5p might be the possible lead compounds for the treatment of diabetes.

A library of twenty-four 2'-aryl-2,5'-bibenzoxazoles (8a-8x) has been synthesized from 2-arylbenzoxazole-5-carboxylic acids (6a-6d) which in turn are obtained by hydrolysis of methyl 2-arylbenzoxazole-5-carboxylates (5a-5d) in excellent yields. These carboxylates (5a-5d) are prepared form methyl 3-amino-4-hydroxybenzoate (3) and readily available various benzoic acids. The bibenzoxazoles (8a-8x) are characterised using NMR, FT-IR and HRMS techniques and the structure of 8h was established by X-ray crystallography. All the synthesized compounds (8a-8x) were screened for cytotoxicity ( in vitro ) against cervical cancer (HeLa) and hepato-carcinoma (HepG2) cell lines and non-cancerous (HEK293) cell line. Compounds, 8p, 8k and 8t shows good activity against HeLa cancer lines having the IC(50 )values 4.787, 9.611 and 10.68 mu M, respectively. (C 2022 Elsevier B.V. All rights reserved.

A range of stereochemically defined oxidative dearomatization products formed by treating 2-(2hydroxyaryl)benzoxazoles and 2-(2-hydroxyaryl)benzothiazoles with phenyliodine(III) diacetate have been described, demonstrating remarkable regiochemical and stereochemical dictated by the nature of the phenol substituents. Benzoxazole-substituted phenols undergo dearomatization leading to the regioand stereoselective synthesis of tetramethoxy-substituted cyclohexenones (4,4,5,6-tetramethoxycyclohex2-en-1-ones). However, benzothiazole-substituted phenols readily undergo regio- and stereoselective [4 + 2] dimerization to bicyclo[2.2.2]octenone. Further, halogenated 2-(2-hydroxyaryl)benzoxazoles lead to formation of a different tetramethoxy-substituted cyclohexenones (2,4,5,6-tetramethoxycyclohex-2-en1-ones) whereas halogenated 2-(2-hydroxyaryl)benzothiazoles afforded 4-methoxycyclohexa-2,5-dien-1ones. The structure of all the compounds were established using NMR, FT-IR and HRMS techniques, and the structure of two compounds were confirmed by X-ray crystallography. (c) 2022 Elsevier B.V. All rights reserved.

2-Halogenatedphenyl benzoxazole-5-carboxylic acids with mono-halogen (chloro, bromo and fluoro) substituted at ortho-, meta- and para-positions on the phenyl ring were designed and synthesized based on significance of presence of halogen in increasing number of marketed halogenated drugs and importance of benzoxazoles. These 2-alogenatedphenylbenzoxazole-5-carboxylic acids and their methyl esters were screened for anti-inflammatory activity, and cytotoxicity. 2-(3-Chlorophenyl)benzoxaole-5-carboxylic acid (6b) exhibited significant anti-inflammatory activity with IC50 values of 0.103 mM almost equivalent to the standard drug ibuprofen (0.101 mM). 2-(4-Chlorophenyl)benzoxaole-5-carboxylic acid (6c) showed excellent cytotoxic activity against 22Rv1 cells (human prostate carcinoma epithelial cell lines) with IC50 value of 1.54 μM better than that of standard drug doxorubicin having IC50 value of 2.32 μM. More importantly, the selectivity index of this potential molecule was found to be 57.74. Molecular docking analysis resulted in good binding interactions of these compounds with their respective biochemical targets viz. Cyclooxygenase-2 and aldo-keto reductase IC3.