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 language | English |
|---|---|
| Pages (from-to) | 6513-6520 |
| Number of pages | 8 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 13 |
| Issue number | 23 |
| DOIs | |
| Publication status | Published - 2005 Dec 1 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
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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 journal › Article
TY - JOUR
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.
AB - 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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U2 - 10.1016/j.bmc.2005.07.018
DO - 10.1016/j.bmc.2005.07.018
M3 - Article
VL - 13
SP - 6513
EP - 6520
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 23
ER -