Tetrazolylmethyl quinolines: design, docking studies, synthesis, anticancer and antifungal analyses

A new series of 2,5 and 1,5-regioisomers of the tetrazolyl group viz., 3-(5-benzyl/benzylthio-2H-tetrazol-2-yl) methyl-2-chloro-6-substituted quinoline 6h-q and 3-(5-benzyl/benzylthio-1H-tetrazol-1-yl) methyl-2-chloro-6-substituted quinolines 7h-q were synthesized. Docking studies of all these compounds with DNA as target using PDB: 1AU5 and 453D revealed that the compounds 6h and 6i act as covalent cross linker on the DNA helix of the former and intercalate the latter both with higher C score values. Another set of docking studies in the active pocket of dihydrofolate reductase and N-myristoyl transferase as targets to assess antifungal activity revealed that compounds 6k, 6l, 6p and 7q (with bromo and fluro substituents) showcases different binding modes and hydrogen bonding. Further, the compounds were screened for anticancer activity (primary cytotoxicity) against NCI-60 Human tumor cell line at a single high dose (10−5 M) concentration assay. Among the tested compounds, 6h has shown 99.28% of GI against Melanoma (SK-MEL-5) and compound 6i has shown 97.56% of GI against Breast Cancer (T-47D). Further, in vitro antifungal assay against A. fumigatus and C. albicans for these compounds 6h-q and 7h-q revealed potential to moderate activities as compared to the standard

Novel 1,2,4-triazole clubbed with 1,3,4-oxadiazole motifs as efficient antimicrobial agents from N-arylsydnone as synthon

1,2,4-Triazoles and 1,3,4-oxadiazoles independently are very important pharmacophores. In view of this, a new class of 1,2,4-triazole clubbed with 1,3,4-oxadiazole motifs have been prepared and characterized by IR, 1H NMR, 13C NMR and mass spectral analysis. Molecular docking of all the title compounds into S. aureus tyrosyl-tRNA synthetase (PDB: 1JIJ) and lanosterol 14α-demethylase complex with standard inhibitor Fluconazole (PDB: 3KHM) was performed which snugly fitted into the active site thus explaining their excellent inhibitory activity exhibiting their possible antibacterial and antifungal activity, respectively. Drug-likeliness, Drug score values and toxicity prediction analyses of all the title compounds have shown favourable values and these molecules belong to Class 4 and Class 5 categories which make them useful scaffolds. Interestingly, the compounds 7h, 7i, 7k, 7u and 7v have exhibited majestic antibacterial activity. Also, these compounds have shown antifungal activity against all pathogenic fungal strains with lower MIC value ranging from 0.50 - 4.00 µg/mL

Analysis of Antibody and Cytokine Markers for Leprosy Nerve Damage and Reactions in the INFIR Cohort in India

Leprosy is one of the oldest known diseases. In spite of the established fact that it is least infectious and a completely curable disease, the social stigma associated with it still lingers in many countries and remains a major obstacle to self reporting and early treatment. The nerve damage that occurs in leprosy is the most serious aspect of this disease as nerve damage leads to progressive impairment and disability. It is important to identify markers of nerve damage so that preventive measures can be taken. This prospective cohort study was designed to look at the potential association of some serological markers with reactions and nerve function impairment. Three hundred and three newly diagnosed patients from north India were recruited for this study. The study attempts to reflect a model of nerve damage initiated by mycobacterial antigens and maintained by ongoing inflammation through cytokines such as Tumour Necrosis Factor alpha and perhaps extended by antibodies against nerve components

Synthesis, spectral characterization and antihaemostatic activity of 1,2,4-triazoles incorporating 1,2,4-triazine rings

A simple and high yielding method for the integration of a 1,2,4-triazole ring with 1,2,4-triazine-5-one (4a-j) has been developed starting from 3-arylsydnones (1a-d). The structures were proved by their spectral data and screened for antihaemostatic activity

Synthesis and pharmacological evaluation of 1,5-benzothiazepine derivatives

A simple method for the synthesis of 1,5-benzothiazepines integrated with 5-methyl-2-oxo-3-phenyl-Δ 4-1,3,4-oxadiazoles in 75–95% yield is devised. A comparison of microwave-accelerated reaction with conventional heating is also illustrated. Structures of all the newly synthesised compounds were characterised by physical, analytical and spectral (UV, IR, 1H NMR, and MS) data. Title compounds were screened for their antimicrobial, anticonvulsant, anti-inflammatory, and diuretic activities

An efficient synthesis of pharmacologically active derivatives of 1,3,4-oxadiazoles

Abstract A simple and environmental friendly microwave irradiation method is devised for the synthesis of derivatives of 1,3,4-oxadiazoles viz., 6a-e and 7h-q in 75–90% yield. Structures of the newly synthesised compounds were confirmed by physical, analytical and spectral (ir, 1H and 13C nmr and ms) data and screened for antiinflammatory, anticonvulsant, antidiuretic and antihaemostatic activities. Some of the compounds have shown potent activities

An efficient synthesis of novel 3’-substituted 2-aryl-5-methyl-5'thioxo-[4,4'-bi-4H-1,2,4-triazol]-3(1'H, 2H)-ones

Asimple and high yieldingmethod for the integration of two 1,2,4-triazole rings (10a–l) has been developed starting from 3-arylsydnones (1a–d). Confirmation for the structures of the newly synthesised compounds was provided by their physical, analytical and spectral data (IR, 1H NMR, 13C NMR and MS)

A rapid and convenient synthetic route to novel 1,5-benzodiazepine derivatives of 5-methyl-3-phenyl-2-oxo-Δ4-1,3,4-oxadiazolines from p-acetylphenylsydnone and their pharmacological activity

Abstract A simple and high yielding method for the integration of 1,5-benzodiazepines integrated with 5-methyl-2-oxo-3-phenyl-Δ4-1,3,4-oxadiazolines in 75%–90% yield by microwave irradiation is devised. Microwave-accelerated reaction was compared with thermal method. All the compounds were characterized by physical, analytical and spectral (IR, 1H NMR, MS) data. Title compounds were screened for preliminary pharmacological activities

Original scientific paper An efficient synthesis of novel 3’-substituted

Abstract: A simple and high yielding method for the integration of two 1,2,4-triazole rings (10a–l) has been developed starting from 3-arylsydnones (1a–d). Confirmation for the structures of the newly synthesised compounds was provided by their physical, analytical and spectral data (IR, 1HNMR, 13CNMRandMS)