Open AccessDESIGN AND SYNTHESIS OF NOVEL 2, 3-DISUBSTITUTED QUINAZOLINES: EVALUATION OF IN VITRO ANTICANCER ACTIVITY AND IN SILICO STUDIES
Author(s) -
Siva Jyothi Buggana,
Mani Chandrika Paturi,
Rajendra Prasad Vvs
Publication year - 2019
Publication title -
asian journal of pharmaceutical and clinical research
Language(s) - English
Resource type - Journals
eISSN - 2455-3891
pISSN - 0974-2441
DOI - 10.22159/ajpcr.2020.v13i1.36215
Subject(s) - quinazoline , chemistry , cytotoxicity , in vitro , cytotoxic t cell , mtt assay , acetamide , stereochemistry , in silico , hela , cancer cell , benzothiazole , docking (animal) , biochemistry , combinatorial chemistry , cancer , biology , organic chemistry , medicine , genetics , gene , nursing
Objective: In this study, a series of novel 2,3-disubstituted quinazolines (4a-4l) were synthesized using standard procedures and elucidated through different spectroscopic techniques.
Methods: Obtained compounds were evaluated for their cytotoxicity against human breast cancer (MDA-MB-231) and ovarian cancer (SK-O-V3) cell lines using MTT assay. Docking studies with JAK2 protein were performed to elucidate the possible mechanistic insights into these novel quinazoline derivatives.
Results: Moderate-to-good in vitro cytotoxic potentials of the newly synthesized molecules were reported against selected human cancer cell lines. Among the tested molecules, compound 4e showed good cytotoxic activity against MD-AMB-231 (14.2 ± 0.86 μM) and against SK-O-V3 (17.7 ± 0.62 μM).
Conclusion: The in vitro studies of the newly synthesized quinazoline derivatives reported considerable cytotoxic potentials against both breast and ovarian cancer cell lines and SAR studies suggest that quinazoline derivatives with heterocyclic benzothiazole nucleus with hydrophilic acetamide linkage at the 3rd position could probably increase the cytotoxic potentials and the presence of chlorine substitution could add more benefit. With the reported bioactivities of these derivatives, further studies on the derivatization could elucidate the broader cytotoxic potentials.