PMID: 11606134Oct 19, 2001Paper

Synthesis and antitumor activity of ester-modified analogues of bengamide B

Journal of Medicinal Chemistry
Frederick R KinderS Zabludoff

Abstract

Bengamide B, a novel sponge-derived marine natural product with broad spectrum antitumor activity, was not suitable for further preclinical development because of its difficult synthesis and very poor water solubility. Bengamide B produced a 31% T/C at its solubility-limited maximum intravenous dose of 33 micromol/kg in MDA-MB-435 breast carcinoma implanted subcutaneously as a xenograft in nude mice. Compound 8a, a bengamide B analogue with three structural changes (t-Bu alkene substituent, unsubstituted lactam nitrogen, and inverted lactam 5'-myristoyloxy group), was as potent as bengamide B in vitro and more efficacious than bengamide B in vivo. A series of ester-modified analogues based on 8a were synthesized and tested in vitro and in vivo (MDA-MB-435). The cyclohexyl- and phenethyl-substituted esters, 8c and 8g, respectively, had in vitro and in vivo activities similar to that of 8a and enhanced water solubility (ca. 1 mg/mL). Consequently, 8c and 8g were tested in the MDA-MB-435 xenograft model at 100 micromol/kg and produced 29% and 57% tumor regression, respectively.

References

Mar 23, 2001·The Journal of Organic Chemistry·Z ThaleP Crews
Apr 13, 2001·The Journal of Organic Chemistry·F R KinderS Zabludoff

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Citations

Jan 1, 1997·Progress in Biophysics and Molecular Biology·M BolognesiP Ascenzi
Aug 24, 2012·Journal of Medicinal Chemistry·Wei XuQi-Zhuang Ye
May 3, 2013·Journal of Medicinal Chemistry·Feiran ZhangJun O Liu
Mar 19, 2013·Marine Drugs·Ying-Qing Wang, Ze-Hong Miao
Mar 22, 2014·Marine Drugs·Cristina García-Ruiz, Francisco Sarabia
Nov 29, 2011·European Journal of Medicinal Chemistry·Jing-Ping LuQi-Zhuang Ye
Dec 30, 2014·Frontiers in Cellular Neuroscience·Bruno A CisternaJuan C Sáez
Feb 10, 2019·Marine Drugs·Matthew T JamisonTadeusz F Molinski
Dec 3, 2014·Chemical & Pharmaceutical Bulletin·Hongxing MaShiqin Sun
Dec 21, 2016·MedChemComm·Thi Dao PhiVan Cuong Pham
Oct 10, 2003·The Journal of Biological Chemistry·Harry TowbinPenny E Phillips
Nov 18, 2010·Organic & Biomolecular Chemistry·Suresh E KurhadeD Srinivasa Reddy
Aug 14, 2010·The Journal of Organic Chemistry·Francisco SarabiaAntonio Sánchez-Ruiz
May 8, 2013·The Journal of Organic Chemistry·Francisco SarabiaCarlos Vivar-García
Aug 28, 2021·Trends in Pharmacological Sciences·Andrea Goya GrocinEdward W Tate
Nov 5, 2005·The Journal of Organic Chemistry·Francisco Sarabia, Antonio Sánchez-Ruiz
Jun 7, 2002·Organic Letters·Robert K BoeckmanBrian C Shook

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