Structure–Activity Relationships of Thiophene Carboxamide Annonaceous Acetogenin Analogs: Shortening the Alkyl Chain in the Tail Part Significantly Affects Their Growth Inhibitory Activity against Human Cancer Cell Lines

• Published in: Chemical & pharmaceutical bulletin Vol. 69; no. 10; pp. 1029 - 1033
• Main Authors: Ohta, Kaito, Akatsuka, Akinobu, Dan, Shingo, Iwasaki, Hiroki, Yamashita, Masayuki, Kojima, Naoto
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 01.10.2021; Pharmaceutical Soc Japan; Japan Science and Technology Agency
• Subjects: Analogs; annonaceous acetogenin; Anticancer properties; Antitumor activity; antitumor agent; Cancer; Chains; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Electron transport chain; Life Sciences & Biomedicine; Mitochondria; NADH-ubiquinone oxidoreductase; organic synthesis; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; structure–activity relationship; Tails; Tetrahydrofuran; Tumor cell lines; THF RING; annonaceous acetogenin; DESIGN; SOLAMINS; organic synthesis; COMPLEX-I; DRUG DISCOVERY; CHEMISTRY; antitumor agent; ANTITUMOR-ACTIVITY; structure-activity relationship
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.c21-00450

In a previous study, we found that the thiophene carboxamide solamin analog, which is a mono-tetrahydrofuran annonaceous acetogenin, showed potent antitumor activity through the inhibition of mitochondrial complex I. In this study, we synthesized analogs with short alkyl chains instead of the n-dodecyl group in the tail part. We evaluated their growth inhibitory activities against human cancer cell lines. We found that the alkyl chain in the tail part plays an essential role in their activity.