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Design, Synthesis and Therapeutic Potential of some 6, 6'-(1,4-phenylene)bis(4-(4-bromophenyl)pyrimidin-2-amine)analogues.
Mini Reviews in Medicinal Chemistry 2018 December 11
A library of 6, 6'-(1,4-phenylene)bis(4-(4-bromophenyl)pyrimidin-2-amine) derivatives has been synthesized by Claisen-Schmidt condensation and its chemical structure was confirmed by FT-IR, 1H/13C-NMR spectral and elemental analyses. The molecular docking study was carried to find the interaction between active bis-pyrimidine compounds with CDK-8 protein. The in vitro antimicrobial potential of the synthesized compounds was determined against Gram-positive and Gram-negative bacteria species as well fungal species by tube dilution technique. Antimicrobial results indicated that compound 11y was found to be most potent one against E. coli (MICec = 0.67 µmol/mL) and C. albicans (MICca = 0.17 µmol/mL) and its activity was comparable to norfloxacin (MIC = 0.47 µmol/mL) and fluconazole (MIC = 0.50 µmol/mL) respectively. Anticancer screening of the synthesized compounds using sulforhodamine B (SRB) assay demonstrated that compounds 2y (IC50 = 0.01 µmol/mL) and 4y (IC50= 0.02 µmol/mL) have high antiproliferative potential against human colorectal carcinoma cancer cell line than the reference compound, 5-fluorouracil and these compounds also showed best dock score with better potency within the ATP binding pocket and may also be used lead for rational drug designing.
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