ABSTRACT
Tuberculosis caused by Mycobacterium tuberculosis remains a leading cause of mortality worldwide into 21st century. In continuation with our anti-tuberculosis research programme, in this work, we have prepared molecularly diverse coumarins clubbed with benzothiazepines as well as its aza-analogues-benzodiazepines by molecular hybridization. The resulting compounds were screened for their M. tuberculosis activity against H(37) Rv strains using microplate alamar blue assay. Among the designed diversity, the compounds 5k, 5n and 5o were found significantly active in primary anti-tuberculosis assay at minimum inhibitory concentration <6.25 µm. Moreover, the IC(50) values of 5k and 5o in level-2 screening were observed as >10 µg/mL and 3.63 µg/mL, respectively. Design and synthesis of more focused library and its three-dimensional quantitative structure activity relationship analysis are underway.
Subject(s)
Antitubercular Agents/chemistry , Azepines/chemistry , Coumarins/chemistry , Mycobacterium tuberculosis/drug effects , Thiazepines/chemistry , Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Coumarins/chemical synthesis , Coumarins/pharmacology , Microbial Sensitivity Tests , Quantitative Structure-Activity Relationship , Thiazepines/chemical synthesis , Thiazepines/pharmacologyABSTRACT
A series of novel N-1,3-benzo[d]thiazol-2-yl-2-(2-oxo-2H-chromen-4-yl)acetamide derivatives has been synthesized. All the newly synthesized compounds were evaluated for their anti-HIV activity using MTT method. Most of these compounds showed moderate to potent activity against wild-type HIV-1 with an EC(50) ranging from >7 EC(50) [µg/ml] to <100 EC(50) [µg/ml]. Among them, N-1,3-benzo[d]thiazol-2-yl-2-(2-oxo-2H-chromen-4-yl)acetamide 6v was identified as the most promising compound (EC(50)=<7 µg/ml). Among all the compounds, three compounds 6m, 6v and 6u have been exhibits potent anti-HIV activity against MT-4 cells.
Subject(s)
Acetamides/chemical synthesis , Acetamides/pharmacology , Anti-Retroviral Agents/chemical synthesis , Anti-Retroviral Agents/pharmacology , HIV-1/drug effects , Acetamides/chemistry , Anti-Retroviral Agents/chemistry , Benzopyrans/chemical synthesis , Benzopyrans/chemistry , Benzopyrans/pharmacology , Benzothiazoles/chemical synthesis , Benzothiazoles/chemistry , Benzothiazoles/pharmacology , Cells, Cultured , Humans , Molecular StructureABSTRACT
An improved and convenient methodology for the synthesis of asymmetrically substituted pyrazines starting from 3,5-dichloropyrazin-2(1H)-ones has been elaborated. Several nucleoside analogues have been synthesized containing the pyrazine core as the organic base coupled with the sugar via a triazole linkage. The beneficial effect of microwave irradiation throughout the sequence has been demonstrated.
Subject(s)
Nucleosides/chemistry , Nucleosides/chemical synthesis , Pyrazines/chemistry , Pyrazines/chemical synthesis , Triazoles/chemistry , Base Sequence , Magnetic Resonance Spectroscopy , Microwaves , Molecular StructureABSTRACT
1,5-Benzothiazepine and 1,5-benzodiazipine are the two main seven-membered heterocyclic ring systems reported for their cardiac and psychotherapeutic activities. Successful introduction of diltiazem and clentiazem for angina pectoris, hypertension, arrhythmias and other related cardiac disorders proved potential of 1,5-benzothiazepine moiety. Subsequently 1,5-benzodiazepines were highlighted as important biologically active scaffolds. Also, discovery of thiazesim and quetiapine fumarate as psychotropic agents attracted much attention worldwide. The current review article focuses on pharmacological profile associated with 1,5-benzodiazepines. This article mainly covers structural modifications done for various targets along with the brief description of the targets.
