title: Synthesis, absolute stereochemistry and molecular design of the new antifungal and antibacterial antibiotic produced by Streptomyces sp.201.
abstract: The absolute stereochemistry of the new antifungal and antibacterial antibiotic produced by Streptomyces sp.201 has been established by achieving the total synthesis of the product. A series of analogues have also been synthesized by changing the side chain and their bioactivity assessed against different microbial strains. Among them, 1e (R = C8H17) was found to be the most potent with MIC of 8 microg/mL against Mycobacterium tuberculosis, 12 microg/mL against Escherichia coli and 16 microg/mL against Bacillus subtilis 6 microg/mL against Proteus vulgaris. This was followed by 1b (R = C5H11) with MIC of 10-20 microg/mL range and 1d (R = C7H15) with MIC of 14-24 g/mL, whereas 1a (R = C4H9) and 1f (R = C18H35) were found to be completely inactive. Besides, 1c (R = C6H13) showed certain extent of antibacterial activity in the range of 24-50 microg/mL. Mycobacterium tuberculosis was very sensitive to 1e (R = C8H17) with MIC of 8 microg/mL. Antifungal activity of analogues 1d (R = C7H15) and 1e, (R = C8H17) against Fusarium oxysporum and Rhizoctonia solani were found promising with MFCs in the 15-18 microg/mL range.
authors.affiliation: Natural Products Chemistry Division, Regional Research Laboratory (CSIR), Jorhat 785006, Assam, India.
authors.forename: J
authors.initials: J
authors.lastname: Boruwa
authors.forename: B
authors.initials: B
authors.lastname: Kalita
authors.forename: N C
authors.initials: NC
authors.lastname: Barua
authors.forename: J C
authors.initials: JC
authors.lastname: Borah
authors.forename: S
authors.initials: S
authors.lastname: Mazumder
authors.forename: D
authors.initials: D
authors.lastname: Thakur
authors.forename: D K
authors.initials: DK
authors.lastname: Gogoi
authors.forename: T C
authors.initials: TC
authors.lastname: Bora
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000494:pharmacology; D000935:Antifungal Agents / Q000378:metabolism* / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005670:Fusarium / Q000187:drug effects; D007539:Isonicotinic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D012232:Rhizoctonia / Q000187:drug effects; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C467052:2-methylheptyl isonicotinate; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D007539:Isonicotinic Acids