Bioorganic & Medicinal Chemistry Letters 2011-08-01

Synthesis, molecular modeling and bio-evaluation of cycloalkyl fused 2-aminopyrimidines as antitubercular and antidiabetic agents.

Nimisha Singh, Sarvesh Kumar Pandey, Namrata Anand, Richa Dwivedi, Shyam Singh, Sudhir Kumar Sinha, Vinita Chaturvedi, Natasa Jaiswal, Arvind Kumar Srivastava, Priyanka Shah, M Imran Siddiqui, Rama Pati Tripathi

Index: Bioorg. Med. Chem. Lett. 21 , 4404-8, (2011)

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Abstract

An economical and efficient one step synthesis of a series of 8-(arylidene)-4-(aryl)-5,6,7,8-tetrahydro-quinazolin-2-ylamines and 9-(arylidene)-4-(aryl)-6,7,8,9-tetrahydro-5H-cycloheptapyrimidin-2-ylamines by the reaction of bis-benzylidene cycloalkanones and guanidine hydrochloride in presence of NaH has been developed. All the synthesized compounds were evaluated against Mycobacterium tuberculosis H(37)Rv strain and the α-glucosidase and glycogen phosphorylase enzymes. Few of the compounds have shown interesting in vitro activity with MIC up to 3.12 μg/mL against M. tuberculosis and very good inhibition of α-glucosidase and glycogen phosphorylase enzymes. The most potent non toxic compound 40 exhibited about 58% ex vivo activity at MIC of 3.12 μg/mL. The present study opens a new gate to synthesize antitubercular agents for diabetic TB patients. In silico docking studies indicate that mycobacterial dihydrofolate reductase is the possible target of these compounds.Copyright © 2011 Elsevier Ltd. All rights reserved.