title: Synthesis, molecular modeling and bio-evaluation of cycloalkyl fused 2-aminopyrimidines as antitubercular and antidiabetic agents.
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.
authors: Medicinal and Process Chemistry Division, Central Drug Research Institute, CSIR, Lucknow, India.
authors: Nimisha
authors: N
authors: Singh
authors: Sarvesh Kumar
authors: SK
authors: Pandey
authors: Namrata
authors: N
authors: Anand
authors: Richa
authors: R
authors: Dwivedi
authors: Shyam
authors: S
authors: Singh
authors: Sudhir Kumar
authors: SK
authors: Sinha
authors: Vinita
authors: V
authors: Chaturvedi
authors: Natasa
authors: N
authors: Jaiswal
authors: Arvind Kumar
authors: AK
authors: Srivastava
authors: Priyanka
authors: P
authors: Shah
authors: M Imran
authors: MI
authors: Siddiqui
authors: Rama Pati
authors: RP
authors: Tripathi
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D011743:Pyrimidines; D011799:Quinazolines; C012180:2-aminopyrimidine; D024981:Glycogen Phosphorylase; D000520:alpha-Glucosidases