title: Tetrazolylmethyl quinolines: Design, docking studies, synthesis, anticancer and antifungal analyses.
abstract: 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 (10-5M) 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.
authors.affiliation: Department of Chemistry, Karnatak University Dharwad, Pavate Nagar, Dharwad, 580 003, Karnataka, India.
authors.forename: Saba Kauser J
authors.initials: SKJ
authors.lastname: Shaikh
authors.affiliation: Department of Chemistry, Karnatak University Dharwad, Pavate Nagar, Dharwad, 580 003, Karnataka, India. Electronic address: kamchem9@gmail.com.
authors.forename: Ravindra R
authors.initials: RR
authors.lastname: Kamble
authors.affiliation: Department of Chemistry, Karnatak University Dharwad, Pavate Nagar, Dharwad, 580 003, Karnataka, India.
authors.forename: Shilpa M
authors.initials: SM
authors.lastname: Somagond
authors.affiliation: Department of Physics, Yuvaraja's College, University of Mysore, Mysore, 570 005, Karnataka, India.
authors.forename: H C
authors.initials: HC
authors.lastname: Devarajegowda
authors.affiliation: Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T.'s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad, 580 002, Karnataka, India.
authors.forename: Sheshagiri R
authors.initials: SR
authors.lastname: Dixit
authors.affiliation: Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T.'s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad, 580 002, Karnataka, India.
authors.forename: Shrinivas D
authors.initials: SD
authors.lastname: Joshi
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: C000617015:3-((5-(benzylthio)-1H-tetrazol-1-yl)methyl)-2-chloro-6-fluoroquinoline; C000617018:3-((5-(benzylthio)-2H-tetrazol-2-yl)methyl)-6-bromo-2-chloroquinoline; C000617017:3-((5-benzyl-2H-tetrazol-2-yl)methyl)-6-bromo-2-chloroquinoline; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D011804:Quinolines; D013777:Tetrazoles
keywords: Anticancer activity; Antifungal screening; DNA; Dihydrofolate reductase; Molecular docking; N-Myristoyl transferase; Quinoline; Regioisomer; Tetrazole