title: Antimycobacterial activity of natural products and synthetic agents: pyrrolodiquinolines and vermelhotin as anti-tubercular leads against clinical multidrug resistant isolates of Mycobacterium tuberculosis.
abstract: Various classes of natural products and synthetic compounds were tested against reference strains and clinical multidrug resistant isolates of Mycobacterium tuberculosis. Vermelhotin (19), a natural tetramic acid from fungi, was the most active toward clinical MDR TB isolates (MIC 1.5-12.5 μg/mL). Synthetic compounds (i.e. benzoxazocines, coumarins, chromenes, and pyrrolodiquinoline derivatives) were prepared by green chemistry approaches. Under microwave irradiation, a one-pot synthesis of pyrrolodiquinoline 85 was achieved by homocoupling of 1-methylquinolinium iodide; the structure of 85 was confirmed by single-crystal X-ray analysis. Compound 85 and its derivative 86 exhibited potent anti-tubercular activity (MIC 0.3-6.2 μg/mL) against clinical MDR TB isolates, and they displayed weak cytotoxicity toward normal cell line. The scaffold of 85 and 86 is potential for antimycobacterial activity.
authors.affiliation: Chulabhorn Graduate Institute, Chemical Biology Program, Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand.
authors.forename: Dakshina U
authors.initials: DU
authors.lastname: Ganihigama
authors.affiliation: Chulabhorn Research Institute, Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand.
authors.forename: Sanya
authors.initials: S
authors.lastname: Sureram
authors.affiliation: Chulabhorn Research Institute, Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand.
authors.forename: Sasithorn
authors.initials: S
authors.lastname: Sangher
authors.affiliation: Division of Microbiology, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Rama VI Road, Bangkok 10400, Thailand.
authors.forename: Poonpilas
authors.initials: P
authors.lastname: Hongmanee
authors.affiliation: Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Thammarat
authors.initials: T
authors.lastname: Aree
authors.affiliation: Chulabhorn Graduate Institute, Chemical Biology Program, Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand; Chulabhorn Research Institute, Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand.
authors.forename: Chulabhorn
authors.initials: C
authors.lastname: Mahidol
authors.affiliation: Chulabhorn Graduate Institute, Chemical Biology Program, Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand; Chulabhorn Research Institute, Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology (EHT), CHE, Ministry of Education, Bangkok, Thailand.
authors.forename: Somsak
authors.initials: S
authors.lastname: Ruchirawat
authors.affiliation: Chulabhorn Graduate Institute, Chemical Biology Program, Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand; Chulabhorn Research Institute, Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology (EHT), CHE, Ministry of Education, Bangkok, Thailand. Electronic address: prasat@cri.or.th.
authors.forename: Prasat
authors.initials: P
authors.lastname: Kittakoop
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D001688:Biological Products; D011759:Pyrrolidines; D011804:Quinolines; C534203:vermelhotin
keywords: Antimycobacterial activity; Antimycobacterial compound; Microwave-assisted synthesis; Multidrug resistant tuberculosis; Mycobacterium tuberculosis; Natural product