title: Total synthesis and in vitro bioevaluation of clavaminols A, C, H & deacetyl clavaminol H as potential chemotherapeutic and antibiofilm agents.
abstract: A highly concise and expedient total synthesis of bioactive clavaminols (1-4) has been executed using commercially available achiral compound decanol. The synthetic strategy relied on trans-Wittig olefination, Sharpless asymmetric epoxidation, regioselective azidolysis and in situ detosylation followed by reduction as key reactions with good overall yield. Based on biological evaluation studies of all the synthesized compounds, it was observed that the clavaminol A (1) exhibited good cytotoxicity against DU145 and SKOV3 cell lines with IC50 value of 10.8 and 12.5 μM, respectively. Clavaminol A (1) and deacetyl clavaminol H (3) displayed selective promising inhibition towards Gram-positive pathogenic bacterial strains and showed good antifungal activity against the tested Candida strains. In addition, compounds 1 and 3 have demonstrated significant bactericidal activity. Compound 3 was found to be equipotent to the standard drug Miconazole displaying MFC value of 15.6 μg/mL against Candida albicans MTCC 854, C. albicans MTCC 1637, C. albicans MTCC 3958 and Candida glabrata MTCC 3019. Compounds 1 and 3 were also able to inhibit the biofilm formation of Micrococcus luteus MTCC 2470 and Staphylococcus aureus MLS16 MTCC 2940. Clavaminol A (1) increased the levels of reactive oxygen species (ROS) accumulation in M. luteus MTCC 2470.
authors.affiliation: Centre for Lipid Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: T
authors.initials: T
authors.lastname: Vijai Kumar Reddy
authors.affiliation: Centre for Lipid Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: A
authors.initials: A
authors.lastname: Jyotsna
authors.affiliation: Centre for Lipid Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India. Electronic address: prabhavathi@iict.res.in.
authors.forename: B L A
authors.initials: BL
authors.lastname: Prabhavathi Devi
authors.affiliation: Centre for Lipid Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: R B N
authors.initials: RB
authors.lastname: Prasad
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: Y
authors.initials: Y
authors.lastname: Poornachandra
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: C
authors.initials: C
authors.lastname: Ganesh Kumar
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D002175:Candida / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000138:chemical synthesis / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D017382:Reactive Oxygen Species / Q000032:analysis
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D002518:Ceramides; D017382:Reactive Oxygen Species; C569126:clavaminol A; C569127:clavaminol C; C553735:clavaminol H
keywords: Antibiofilm; Antimicrobial; Clavaminols; Cytotoxic; Reactive oxygen species