Synthesis and antitubercular activity of new 1,3,4-oxadiazoles bearing pyridyl and thiazolyl scaffolds.
In search of more potent and safe new antitubercular agents, here new 2-pyridinyl substituted thiazolyl-5-aryl-1,3,4-oxadiazoles (6a-o), have been designed and synthesized using thionicotinamide as a starting, following novel multistep synthetic route. An intermediate, pyridinyl substituted thiazolyl acid hydrazide (4) when condensed with benzoic acids/nicotinic acids (5a-o) in the presence of silica supported POCl3 yielded better to excellent yields of the title compounds. All the synthesized compounds (6a-o) and intermediate acid hydrazide (4) have been screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG. Amongst them, 6f, 6j, 6l and 6o have revealed promising activity against M. bovis BCG at concentrations less than 3μg/mL. These compounds have shown low cytotoxicity (CC50: >100μg/mL) towards four human cancer cell lines. Molecular docking study has also been performed against mycobacterial enoyl reductase (InhA) enzyme to gain an insight into the binding modes of these molecules and recorded good binding affinity. The ADME properties the title products have also been analyzed.
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004, India.
Sambhaji T
ST
Dhumal
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004, India.
Amarsinh R
AR
Deshmukh
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004, India.
Manisha R
MR
Bhosle
Combi Chem-Bio Resource Centre, CSIR-National Chemical Laboratory, Pune 411008, India.
Vijay M
VM
Khedkar
Combi Chem-Bio Resource Centre, CSIR-National Chemical Laboratory, Pune 411008, India.
Laxman U
LU
Nawale
Combi Chem-Bio Resource Centre, CSIR-National Chemical Laboratory, Pune 411008, India.
Dhiman
D
Sarkar
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004, India. Electronic address: manera2011@gmail.com.
Ramrao A
RA
Mane
D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009163:Mycobacterium bovis / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000995:Antitubercular Agents
1,3,4-Oxadiazole; Antitubercular activity; Cytotoxicity; Molecular docking; Pyridine; Thiazole