5-Nitrofuran-2-yl derivatives: synthesis and inhibitory activities against growing and dormant mycobacterium species.
Eighteen 5-nitrofuran-2-yl derivatives were prepared by reacting 5-nitro-2-furfural with various (sub)phenyl/pyridyl thiosemicarbazide using microwave irradiation. The compounds were tested for their in vitro activity against tubercular and various non-tubercular mycobacterium species in log-phase and 6-week-starved cultures. Compound N-(3,5-dibromopyridin-2-yl)-2-((5-nitrofuran-2-yl)methylene)hydrazinecarbothioamide (4r) was found to be the most potent compound (MIC: 0.22 microM) and was 3 times more active than standard isoniazid (INH) and equally active as rifampicin (RIF) in log-phase culture of Mycobacterium tuberculosis H37Rv. In starved M. tuberculosis H37Rv, 4r inhibited with MIC of 13.9 microM and was found to be 50 times more active than INH and slightly more active than RIF.
Sriram
Dharmarajan
D
Medicinal Chemistry & Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science, Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, Andhra Pradesh 500 078, India. drdsriram@yahoo.com
Yogeeswari
Perumal
P
Dhakla
Prathiba
P
Senthilkumar
Palaniappan
P
Banerjee
Debjani
D
Manjashetty
Thimmappa H
TH
D000995:Antitubercular Agents / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009581:Nitrofurans; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014376:Tuberculosis / Q000382:microbiology
D000995:Antitubercular Agents; C538869:N-(3,5-dibromopyridin-2-yl)-2-((5-nitrofuran-2-yl)methylene)hydrazinecarbothioamide; D009581:Nitrofurans; D013882:Thiosemicarbazones