title: Synthesis, QSAR and anticandidal evaluation of 1,2,3-triazoles derived from naturally bioactive scaffolds.
abstract: In the present study, we used eight natural precursors (1a-h) with most of them having promising antimicrobial activities and synthesised their novel 1,2,3-triazole derivatives (3a-h). In the reaction sequences, the precursor compounds (1a-h) were converted to their respective alkyne (2a-h) followed by addition of benzyl azide freshly prepared by the reaction of benzyl bromide with sodium azide using [3 + 2] azide-alkyne cycloaddition strategy. Structural elucidation of all the triazole derivatives was done using FT-IR, (1)H, (13)C NMR, mass and elemental analysis techniques. The single crystal X-ray diffraction for 3d was also recorded. The result of in vitro anticandidal activity performed against three different strains of Candida showed that compound 3e was found superior/comparable to fluconazole (FLC) with IC50 values of 0.044 μg/mL against Candida albicans (ATCC 90028), 12.022 μg/mL against Candida glabrata (ATCC 90030), and 3.60 μg/mL against Candida tropicalis (ATCC 750). Moreover, at their IC50 values, compounds 3e and 3h showed <5% hemolysis which indicates the non-toxic behaviour of these inhibitors. Cytotoxicity assay was also performed on VERO cell line and all the derivatives were found non-toxic up to the concentration of 10.0 μg/mL. The in silico technique of 3D-QSAR was applied to establish structure activity relationship of the synthesized compounds. The results reveal the molecular fragments that play an essential role in improving the anticandidal activity.
authors: Medicinal Chemistry Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India; Medical Mycology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.
authors: Mohammad
authors: M
authors: Irfan
authors: Medicinal Chemistry Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.
authors: Babita
authors: B
authors: Aneja
authors: Department of Physics, Deen Dayal Upadhyay Gorakhpur University, Gorakhpur, UP 273009, India.
authors: Umesh
authors: U
authors: Yadava
authors: National Center for Natural Products Research (NCNPR), School of Pharmacy, University of Mississippi, MS 38677, USA.
authors: Shabana I
authors: SI
authors: Khan
authors: Medical Mycology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.
authors: Nikhat
authors: N
authors: Manzoor
authors: Organisch-Chemisches Institut, Westfalische Wilhelm-Universitat Munster, 48149, Germany.
authors: Constantin G
authors: CG
authors: Daniliuc
authors: Medicinal Chemistry Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India. Electronic address: mabid@jmi.ac.in.
authors: Mohammad
authors: M
authors: Abid
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002176:Candida albicans / Q000187:drug effects*; D041022:Candida tropicalis / Q000187:drug effects*; D060326:Chemistry Techniques, Synthetic; D002522:Chlorocebus aethiops; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D021281:Quantitative Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014709:Vero Cells
chemical_list: D000935:Antifungal Agents; D014230:Triazoles
keywords: Candida; Cytotoxicity; Fluconazole; Hemolysis; QSAR; Triazole; X-ray diffraction