Chemical transformation and biological studies of marine sesquiterpene ( S)-(+)-curcuphenol and its analogs

• Published in: Biochimica et biophysica acta Vol. 1770; no. 11; pp. 1513 - 1519
• Main Authors: Gul, Waseem, Hammond, Nicholas L., Yousaf, Muhammad, Peng, Jiangnan, Holley, Andy, Hamann, Mark T.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2007
• Subjects: Animals; Anti-HIV Agents - pharmacokinetics; Anti-HIV Agents - pharmacology; Antimalarials - pharmacokinetics; Antimalarials - pharmacology; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Antiprotozoal Agents - pharmacokinetics; Antiprotozoal Agents - pharmacology; Antitubercular Agents - pharmacokinetics; Antitubercular Agents - pharmacology; Biotransformation; Cell Line, Tumor; Curcuphenol; Esterification; HIV-1 - drug effects; Humans; Leishmania; Malaria; Marine natural products; Microbial Sensitivity Tests; Porifera; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacokinetics; Sesquiterpenes - pharmacology; Curcuphenol; Malaria; Marine natural products; Leishmania
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2007.05.011

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 μM, respectively. Analog f showed enhanced activity against L. donovani with an IC 50 of 0.6 μM and IC 90 of 40 μM respectively.