Boronic Analogues of (R)-6-O-Desmethylantofine as Anticancer Agents

• Published in: Chemical & pharmaceutical bulletin Vol. 67; no. 12; pp. 1324 - 1327
• Main Authors: Omran, Ziad, Abdalla, Ashraf N., Ibrahim, Munjed M., Hossain, Mohammad A., Alarja, Mohamed, Chen, Linwei, Liu, Yuxiu, Wang, Qingmin
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01-12-2019; Japan Science and Technology Agency
• Subjects: Alkaloids; Anticancer properties; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; Antitumor agents; antofine; Biotechnology; Boron; Boronic Acids - chemistry; Boronic Acids - pharmacology; boronic bioisostere; Cancer; Cell Proliferation - drug effects; Clinical trials; Cytotoxicity; Dose-Response Relationship, Drug; Drug resistance; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Neurotoxicity; phenanthroindolizidine; Structure-Activity Relationship; Toxicity; Tumor cell lines; Tumor Cells, Cultured; boronic bioisostere; cancer; antitumor activity; phenanthroindolizidine; antofine
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.c19-00692

Phenanthroindolizidines are naturally occurring alkaloids mainly isolated from different species of Asclepiadaceae. These alkaloids are characterized by an excellent anticancer activity against a very wide range of cancerous cell lines including those who are multi drug resistant. Nevertheless, phenanthroindolizidines are associated with sever neurotoxicity that prevented any candidate from this family to pass the clinical trials. A number of boron-based analogues of (R)-6-O-desmethylantofine have been synthesised. Their physochemical properties were evaluated, same as their in-vitro antiproliferative activity. The pinacol boronate ester derivative (3) showed interesting cytotoxicity against a panel of cancerous cell lines attested by a cancer cell growth-inhibitory potency (GI50) as low as 30 nM.