Synthesis and antitumor activity of 5-(9-acridinylamino)anisidine derivatives
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Дата
2005
Автори
Bacherikov, Valeriy A.
Назва журналу
ISSN журналу
Назва тому
Видавець
Анотація
A series of 5-(9-acridinylamino)anisidines were synthesized by condensing methoxy-substituted 1,3-phenylenediamines
(10 and 11) with 9-chloroacridine derivatives to form 5-(9-acridinylamino)-m-anisidines (AMAs, 14a–e) and 5-(9-acridinylamino)-o-anisidines (AOAs, 15a–e). 5-(9-Acridinylamino)-p-anisidines (APAs, 17a–e) were synthesized by reacting 2-methoxy-5-nitroaniline (12) with 9-anilinoacridines, followed by reduction. The cytotoxic inhibition of growth of various human tumor cells in
culture, inhibitory effects against topoisomerase II, and DNA interaction of these agents were studied. The structure–activity relationship studies revealed the following degree of potency: AOAs > AMAs > APAs. They also revealed that the newly synthesized
derivatives bearing CONH2NH2NMe2 and Me substituents at C4 and C5 positions of the acridine chromophore (i.e., AMA 14e,
AOA 15e, and APA 17e) exhibited significant cytotoxicity against human tumor cell growth in vitro. AOA (15e) was the most potent
among these derivatives, which resulted in 60% suppression of tumor volume at a dose of 20 mg/kg (Q2D · 9), intravenous injection
on day 26 in nude mice bearing human breast carcinoma MX-1 xenografts.
Бібліографічний опис
Bacherikov Valeriy A. Synthesis and antitumor activity of 5-(9-acridinylamino) anisidine derivatives / Bacherikov Valeriy A., Jang-Yang Chang, etc. // Bioorganic & Medicinal Chemistry. – 2005. – №13. – P. 1-8.
Ключові слова
Acridines, Antitumor compounds, Synthesis, Chemotherapy, Substituent effects
Цитування
Bacherikov Valeriy A. Synthesis and antitumor activity of 5-(9-acridinylamino) anisidine derivatives / Bacherikov Valeriy A., Jang-Yang Chang, etc. // Bioorganic & Medicinal Chemistry. – 2005. – №13. – P. 1-8.