In silico Physicochemical Bioactivities and Toxicities Prediction of 3-chloro-6-arylpyridazines and 6-aryl-4,5-dihydropyridazine-3(2H)-thiones having Anti-tubercular Activity

RGUHS Journal of Pharmaceutical Sciences

Mohammad Asif¹  Mrityunjoy Acharya²  Anita Singh³  Lakshmayya² 

[1] Department of Pharmacy, GRD (P.G) Institute of Management and Technology, 214-Rajpur Road, Dehradun, (U.K), India.Department of Pharmacy, Kumaun University, Bheemtal, Nainital, (U.K), India.Department of Pharmacy, GRD (P.G) Institute of Management and Technology, 214-Rajpur Road, Dehradun, (U.K), India.Department of Pharmacy, GRD (P.G) Institute of Management and Technology, 214-Rajpur Road, Dehradun, (U.K), India.Department of Pharmacy, Kumaun University, Bheemtal, Nainital, (U.K), India.Department of Pharmacy, Kumaun University, Bheemtal, Nainital, (U.K), India.Department of Pharmacy, GRD (P.G) Institute of Management and Technology, 214-Rajpur Road, Dehradun, (U.K), India.Department of Pharmacy, Kumaun University, Bheemtal, Nainital, (U.K), India.;Department of Pharmacy, GRD (P.G) Institute of Management and Technology, 214-Rajpur Road, Dehradun, (U.K), India.Department of Pharmacy, GRD (P.G) Institute of Management and Technology, 214-Rajpur Road, Dehradun, (U.K), India.Department of Pharmacy, GRD (P.G) Institute of Management and Technology, 214-Rajpur Road, Dehradun, (U.K), India.;Department of Pharmacy, Kumaun University, Bheemtal, Nainital, (U.K), India.Department of Pharmacy, Kumaun University, Bheemtal, Nainital, (U.K), India.Department of Pharmacy, Kumaun University, Bheemtal, Nainital, (U.K), India.

关键词: ADME;    Anti-tubercular;    In silico;    Pyridazine;    Physicochemical parameters.;   

DOI  :  10.5530/rjps.2015.2.7

学科分类：药学、药理学、毒理学（综合）

来源: Rajiv Gandhi University of Health Sciences

【 摘 要 】

Purpose: In the present study, antitubercular activities and in silico physicochemical toxicities and bioactivity profile of some 3-chloro-6-arylpyridazines (3a-d) and 6-aryl-4,5-dihydropyridazine-3(2H)-thiones (4a-d) are studied. Approach: The compounds (3a-d) and (4a-d) were evaluated as antitubercular agents against Mycobacterium tuberculosis H37Rv by screening through in vitro Microplate Alamar Blue Assay (MABA) method. Findings: In silico physicochemical parameter revealed that the entire compounds follow Lipinski’s rule-of-5 to become a “drug like” molecule. ADME (absorption, distribution, metabolism and excretions) profile prediction has shown that all the compounds can be absorbed through human intestine (HIA+), Caco-2 cell (Caco-2+) and can cross blood brain barrier (BBB+), they all are non-substrate and non-inhibitor of p-glycoprotein. Compounds 4a-d are inhibitor of human microsomal enzyme like CYP 450 1A2, CYP 450 2C19 and CYP 450 3A4. Research limitations/implications: Compounds 4a-4d are better ligand for enzyme inhibition than 3a-d compounds. The MIC of compounds 4a-d and 3a is 6.25 μg/ml. They are potent than compound 3b-d with MIC 12.5 μg/ml. Originality: Toxicity prediction indicated that compounds 3a-3d and 4a-d are non-carcinogenic and non-mutagenic. Bioactivity prediction for compounds 3a-3d and 4a-d indicated better ligand as enzyme inhibitor in comparison to standard.

【 授权许可】

Unknown