☆ 4.5 Article

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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2011)

期刊

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷 21, 期 15, 页码 4404-4408

出版社

PERGAMON-ELSEVIER SCIENCE LTD

DOI: 10.1016/j.bmcl.2011.06.040

关键词

Cycloalkyl fused 2-aminopyrimidines; bis-Benzylidenecycloalkanones; alpha-Glucosidase inhibitor; Glycogen phosphorylase inhibitor; Antitubercular agents; DHFR inhibitor

类别

Chemistry, Medicinal Chemistry, Organic

资金

DRDO New Delhi
CSIR New Delhi
DBT New Delhi

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摘要

An economical and efficient one step synthesis of a series of 8-(arylidene)-4-(aryl)-5,6,7,8-tetrahydroquinazolin-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 a-glucosidase and glycogen phosphorylase enzymes. Few of the compounds have shown interesting in vitro activity with MIC up to 3.12 mu g/mL against M. tuberculosis and very good inhibition of a-glucosidase and glycogen phosphorylase enzymes. The most potent non toxic compound 40 exhibited about 58% ex vivo activity at MIC of 3.12 mu g/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. (C) 2011 Elsevier Ltd. All rights reserved.

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