Chemical transformation and biological studies of marine sesquiterpene (S)-(+)-curcuphenol and its analogs.
Chemical transformation studies of the marine sesquiterpene phenol (S)-(+)-curcuphenol (1), isolated from the Jamaican sponges Myrmekioderma styx, were accomplished. In order to optimize the activity and better understand the SAR of (S)-(+)-curcuphenol, nineteen semisynthetic analogs were prepared and evaluated for activity against infectious diseases. A number of analogs showed significant activity against Mtb and Leishmania donovani, while showed good to moderate activities in antibacterial and antifungal assays as well as against Plasmodium falciparium (D6 clone) and (W2 clone). The analogs a, c, h, and r exhibited Mtb activity with MICs of 24.6, 41.2, 6.90, and 50.5 microM, respectively. Analog f showed enhanced activity against L. donovani with an IC50 of 0.6 microM and IC90 of 40 microM respectively.
Gul
Waseem
W
Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
Hammond
Nicholas L
NL
Yousaf
Muhammad
M
Peng
Jiangnan
J
Holley
Andy
A
Hamann
Mark T
MT
D000818:Animals; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D000962:Antimalarials / Q000493:pharmacokinetics / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D000995:Antitubercular Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001711:Biotransformation; D045744:Cell Line, Tumor; D004951:Esterification; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D011161:Porifera; D012717:Sesquiterpenes / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*