title: Synthesis and antibacterial evaluation of macrocyclic diarylheptanoid derivatives.
abstract: Bacterial infections, caused by Mycobacterium tuberculosis and other problematic bacterial pathogens, continue to pose a significant threat to global public health. As such, new chemotype antibacterial agents are desperately needed to fuel and strengthen the antibacterial drug discovery and development pipeline. As part of our antibacterial research program to develop natural product-inspired new antibacterial agents, here we report synthesis, antibacterial evaluation, and structure-activity relationship studies of an extended chemical library of macrocyclic diarylheptanoids with diverse amine, amide, urea, and sulfonamide functionalities. Results of this study have produced macrocyclic geranylamine and 4-fluorophenethylamine substituted derivatives, exhibiting moderate to good activity against M. tuberculosis and selected Gram-positive bacterial pathogens.
authors.affiliation: Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, 34 Rainbow Drive, Hilo, HI 96720, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS#1000, Memphis, TN 38105, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Bruhn
authors.affiliation: Department of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS#1000, Memphis, TN 38105, USA.
authors.forename: Marcus M
authors.initials: MM
authors.lastname: Maddox
authors.affiliation: Department of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS#1000, Memphis, TN 38105, USA.
authors.forename: Aman P
authors.initials: AP
authors.lastname: Singh
authors.affiliation: Department of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS#1000, Memphis, TN 38105, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Lee
authors.affiliation: Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, 34 Rainbow Drive, Hilo, HI 96720, USA. Electronic address: dianqing@hawaii.edu.
authors.forename: Dianqing
authors.initials: D
authors.lastname: Sun
mesh_terms: D000588:Amines / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006536:Heptanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry; D014508:Urea / Q000737:chemistry
chemical_list: D000588:Amines; D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D006536:Heptanes; D047028:Macrocyclic Compounds; D013449:Sulfonamides; D014508:Urea
keywords: Antibacterial; Antituberculosis; Diarylheptanoid; Macrocycle; SAR