Synthesis and in vitro biological evaluation of ring B abeo-sterols as novel inhibitors of Mycobacterium tuberculosis.
A series of 3beta-hydroxy steroid analogues possessing a contracted cyclopentane B-ring were prepared based on the initial activity screening of a recently reported naturally occurring marine 5(6-->7)abeo-sterol against Mycobacterium tuberculosis. All of the novel ring B abeo-sterols synthesized showed good inhibitory activity, whereas none of the starting steroids based on the common 3beta-hydroxy-Delta(5)-cholestane nucleus, proved to be active. Therefore, the 5(6-->7)abeo-sterol nucleus present in compounds 3, 5, 7, 9, and 11 represents a novel scaffold for the development of new antitubercular agents.
Wei
Xiaomei
X
Department of Chemistry, University of Puerto Rico, PO Box 23346, UPR Station, San Juan, PR.
Rodríguez
Abimael D
AD
Wang
Yuehong
Y
Franzblau
Scott G
SG
D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002776:Cholestanes / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D011161:Porifera; D013261:Sterols / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
D000995:Antitubercular Agents; D002776:Cholestanes; D013261:Sterols