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Dr.Siddique Akber Ansari

Associate Professor

Associate Professor

كلية الصيدلة
Department of Pharmaceutical Chemistry, College of Pharmacy building 23, King Saud University, P.O. Box 2457, Riyadh 11451,Saudi Arabia
المنشورات
مقال فى مجلة
2019

Identification of Promising Biofilm Inhibitory and Cytotoxic Quinazolin-4-one Derivatives: Synthesis, Evaluation, Molecular Docking and ADMET Studies

A library of 2,3-dihydroquinazolin-4(1H)-one derivatives (5a-k) were synthesized in good yield by using 1-Ethyl-3-Methylimidazolium hydrogen sulphate (10 mol%) as a catalyst and were evaluated for their anti-biofilm, antimicrobial and cytotoxicity potential. Among the synthesized compounds, 2-(4-(1H-1,2,4-triazol-1-yl)phenyl)-2,3-dihydroquinazolin-4(1H)-one (5d) and 2,3-dihydro-2-(2,4,6-trimethoxyphenyl) quinazolin-4(1H)-one (5j) displayed better anti-biofilm activity than fluconazole (IC50 = 40 μM) with IC50 values less than 30 μM. Compound 5d also appeared to be fungicidal against C. Albicans having MIC=33.5 μg/ml comparable with standard fluconazole (50 μg/ml). All the synthesized compounds were also evaluated for cytotoxic activity by using MTT assay against HeLa, A-549 and MDA-MB-231 cell lines. The compound 5d was found to be more potent against MDA-MB-231 and A549 cell lines (IC50 = 11 +_ 2 μM and 34+_8 μM respectively) than 5-fluorouracil (IC50 = 19 +_ 3 μM and 51+_ 5 μM respectively). The compounds substituted with 6-methyl-4-oxo-4H-chromen-3-yl (5a), biphenyl (5c) and 2-hydroxy-5-bromophenyl (5e) were also found to be more potent against MDA-MB-231 cell lines (IC50 = 13 +_ 3 – 14 � 4μM) than 5-fluorouracil. Molecular docking simulations were also carried out using secreted aspartyl protease (SAP5), pepAenzyme of C. albicans for biofilm inhibition and EGFR tyrosine kinase for cyto-toxicity studies. The study reveals that thecompounds 5d and 5e can serve as an important lead moiety for biofilm inhibition and cyto-toxicity against MDA-MB-231 and A549 cancer cell-lines indicating their potential in the treatment of tougher fungal infections and breast and lung cancer.

رقم المجلد
4
رقم الانشاء
2019
الصفحات
1-9
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