ABSTRACT
In the present study, a series of novel 2-[4-(1H-[1,2,4]-triazol-1-yl)phenyl]-1-substituted-4,6-difluoro-1H-benzo[d]imidazole derivatives are synthesized by the alkylation of 2-[4-(1H-[1,2,4]-triazol-1-yl)phenyl]-4,6-difluoro-1H-benzo[d]imidazole with substituted alkyl and aryl halides. The compounds were evaluated for their preliminary in-vitro antibacterial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Salmonella typhosa and then were screened for their antitubercular activity against Mycobacterium tuberculosis H37Rv strain by broth microdilution assay method. The antibacterial data suggested that the analogs with electronegative substituents emerged as promising antimicrobials. It was also observed that the promising antimicrobials have proved to be better antimycobacterials. Few of selected analogs are under further evaluation for secondary antitubercular screening, as they have shown better activity compared to rifampin.
Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Benzimidazoles/chemistry , Benzimidazoles/pharmacology , Mycobacterium tuberculosis/drug effects , Triazoles/chemistry , Anti-Infective Agents/chemical synthesis , Antitubercular Agents/chemical synthesis , Antitubercular Agents/chemistry , Antitubercular Agents/pharmacology , Benzimidazoles/chemical synthesis , Structure-Activity RelationshipABSTRACT
Based on the earlier results of our in-house database and compound library, a series of novel clubbed thienyl triazoles was designed which may emerge as potential cdk5/p25 inhibitors, for the treatment of Alzheimer's disease. A benign synthesis was planned so as to take an advantage of MAOS (Microwave Assisted Organic Synthesis) method. Evaluation of the SAR of this series has allowed the identification of compounds 4, 5, 7 and 8 from series I while 13, 14, 16 and 17 from series II as significant cdk5/p25 inhibitors and thus have potential as possible treatments for Alzheimer's disease.
Subject(s)
Brain/drug effects , Cyclin-Dependent Kinase 5/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Nerve Tissue Proteins/antagonists & inhibitors , Thiazoles/pharmacology , Ticrynafen/chemistry , Alzheimer Disease/drug therapy , Alzheimer Disease/pathology , Brain/metabolism , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/therapeutic use , Humans , Microwaves , Structure-Activity Relationship , Thiazoles/chemical synthesisABSTRACT
In the present study, a series of N-{4-[(4-amino-5-sulfanyl-4H-1,2,4-triazol-3-yl)methyl]-1,3-thiazol-2-yl}-2-substituted-amide (1a-d) derivatives were synthesized in good yields and characterized by IR, 1H NMR, mass spectral and elemental analyses. The compounds were evaluated for their preliminary in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhosa and then were screened for antitubercular activity against Mycobacterium tuberculosis H37 Rv strain by broth microdilution assay method. The antibacterial data of the tested compounds indicated that most of the synthesized compounds showed better activity against bacteria compared to reference drugs. The in vitro antitubercular activity reports of tested compounds against M. tuberculosis strain H37 Rv showed moderate to better activity.
Subject(s)
Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , Thiazoles/chemical synthesis , Thiazoles/pharmacology , Antitubercular Agents/chemistry , Magnetic Resonance Spectroscopy , Mass Spectrometry , Microbial Sensitivity Tests , Thiazoles/chemistryABSTRACT
A novel clubbed triazolyl thiazole series of cdk5/p25 inhibitors, potentially useful for the treatment of Alzheimer's disease, is disclosed. Evaluation of the SAR of substitution within these series has allowed the identification of a range of compounds which significantly reduce brain cdk5/p25 and thus have potential as possible treatments for Alzheimer's disease.
