Design, Synthesis and Therapeutic Potential of Some 6, 6'-(1,4- phenylene)bis(4-(4-bromophenyl)pyrimidin-2-amine)analogues

Author(s): Sanjiv Kumar, Balasubramanian Narasimhan*, Siong Meng Lim, Kalavathy Ramasamy, Vasudevan Mani, Syed Adnan Ali Shah.

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 19 , Issue 7 , 2019

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Abstract:

Background: A series of 6, 6'-(1,4-phenylene)bis(4-(4-bromophenyl)pyrimidin-2-amine) derivatives has been synthesized by Claisen-Schmidt condensation and its chemical structures was confirmed by FT-IR, 1H/13C-NMR spectral and elemental analyses. The molecular docking study was carried out 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 bacterial 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.

Conclusion: 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 drug (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.

Keywords: Antimicrobial, antiproliferative, bis-pyrimidines, molecular docking, synthesis, C. albicans.

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Article Details

VOLUME: 19
ISSUE: 7
Year: 2019
Page: [609 - 621]
Pages: 13
DOI: 10.2174/1389557519666181210162413
Price: $58

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