Synthesis and antitumor activity of 5-(9-acridinylamino)anisidine derivatives

Valeriy A. Bacherikov, Jang-Yang Chang, Yi Wen Lin, Ching Huang Chen, Wen Yu Pan, Huajin Dong, Rong Zau Lee, Ting Chao Chou, Tsann Long Su

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6513-6520
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume13
Issue number23
DOIs
Publication statusPublished - 2005 Dec 1

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Bearings (structural)
Tumors
Derivatives
Acridines
Type II DNA Topoisomerase
Cell growth
Structure-Activity Relationship
Chromophores
Cytotoxicity
Growth
Tumor Burden
Cell culture
Heterografts
Nude Mice
Intravenous Injections
Neoplasms
Cell Culture Techniques
Cells
Breast Neoplasms

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Bacherikov, V. A., Chang, J-Y., Lin, Y. W., Chen, C. H., Pan, W. Y., Dong, H., ... Su, T. L. (2005). Synthesis and antitumor activity of 5-(9-acridinylamino)anisidine derivatives. Bioorganic and Medicinal Chemistry, 13(23), 6513-6520. https://doi.org/10.1016/j.bmc.2005.07.018
Bacherikov, Valeriy A. ; Chang, Jang-Yang ; Lin, Yi Wen ; Chen, Ching Huang ; Pan, Wen Yu ; Dong, Huajin ; Lee, Rong Zau ; Chou, Ting Chao ; Su, Tsann Long. / Synthesis and antitumor activity of 5-(9-acridinylamino)anisidine derivatives. In: Bioorganic and Medicinal Chemistry. 2005 ; Vol. 13, No. 23. pp. 6513-6520.
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abstract = "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.",
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Bacherikov, VA, Chang, J-Y, Lin, YW, Chen, CH, Pan, WY, Dong, H, Lee, RZ, Chou, TC & Su, TL 2005, 'Synthesis and antitumor activity of 5-(9-acridinylamino)anisidine derivatives', Bioorganic and Medicinal Chemistry, vol. 13, no. 23, pp. 6513-6520. https://doi.org/10.1016/j.bmc.2005.07.018

Synthesis and antitumor activity of 5-(9-acridinylamino)anisidine derivatives. / Bacherikov, Valeriy A.; Chang, Jang-Yang; Lin, Yi Wen; Chen, Ching Huang; Pan, Wen Yu; Dong, Huajin; Lee, Rong Zau; Chou, Ting Chao; Su, Tsann Long.

In: Bioorganic and Medicinal Chemistry, Vol. 13, No. 23, 01.12.2005, p. 6513-6520.

Research output: Contribution to journalArticle

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T1 - Synthesis and antitumor activity of 5-(9-acridinylamino)anisidine derivatives

AU - Bacherikov, Valeriy A.

AU - Chang, Jang-Yang

AU - Lin, Yi Wen

AU - Chen, Ching Huang

AU - Pan, Wen Yu

AU - Dong, Huajin

AU - Lee, Rong Zau

AU - Chou, Ting Chao

AU - Su, Tsann Long

PY - 2005/12/1

Y1 - 2005/12/1

N2 - 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.

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