Novel bifunctional alkylating agents, 5,10-dihydropyrrolo[1,2-b] isoquinoline derivatives, synthesis and biological activity Journal Article
| Authors: | Chaniyara, R.; Kapuriya, N.; Dong, H.; Lee, P. C.; Suman, S.; Marvania, B.; Chou, T. C.; Lee, T. C.; Kakadiya, R.; Shah, A.; Su, T. L. |
| Article Title: | Novel bifunctional alkylating agents, 5,10-dihydropyrrolo[1,2-b] isoquinoline derivatives, synthesis and biological activity |
| Abstract: | A series of linear pyrrolo[1,2-b]isoquinoline derivatives was synthesized for antitumor evaluation. The preliminary antitumor studies reveal that both bis(hydroxymethyl) and their bis(alkylcarbamate) derivatives show significant antitumor activity in inhibiting various human tumor cell growth in vitro. 1,2-Bis(hydroxymethyl)-3-methyl-5,10-dihydropyrrolo[1,2-b]isoquinoline (20a) was selected for antitumor studies in animal models. The results show that this agent can induce complete tumor remission or significant suppression in nude mice bearing human breast (MX-1) xenograft and ovarian (SK-OV-3) xenografts, respectively. Alkaline agarose gel shifting assay showed that 20a is able to cross-link with DNA. Studies on the cell cycle inhibition revealed that this agent induces cell arrest at G2/M phase. The results warrant further antitumor investigation against other human tumor growth in animal models. © 2010 Elsevier Ltd. All rights reserved. |
| Keywords: | controlled study; unclassified drug; human cell; nonhuman; mouse; cell cycle; animal experiment; animal model; alkylating agent; antineoplastic activity; cytotoxicity; in vitro study; tumor regression; tumor xenograft; drug synthesis; animalia; mus musculus; cancer inhibition; biological activity; nude mouse; cell cycle g2 phase; cell cycle m phase; antitumor agents; structure-activity relationships; dna cross linking; dna interstrand cross-linking; pyrrolo[1,2-b]isoquinoline; 1,2 bis(hydroxymethyl) 3 methyl 5,10 dihydropyrrolo[1,2 b]isoquinoline; [3 (4 methoxyphenyl) 5,10 dihydropyrrolo[1,2 b]isoquinoline 1,2 diyl]bis(methylene)bis(isopropylcarbamate); [3 (4 methoxyphenyl) 5,10 dihydropyrrolo[1,2 b]isoquinoline 1,2 diyl]dimethanol; [3 methyl 5,10 dihydropyrrolo[1,2 b]isoquinoline 1,2 diyl]bis(methylene)bis (ethylcarbamate); agarose; isoquinoline derivative |
| Journal Title: | Bioorganic & Medicinal Chemistry |
| Volume: | 19 |
| Issue: | 1 |
| ISSN: | 0968-0896 |
| Publisher: | Pergamon-Elsevier Science Ltd |
| Date Published: | 2011-01-01 |
| Start Page: | 275 |
| End Page: | 286 |
| Language: | English |
| DOI: | 10.1016/j.bmc.2010.11.030 |
| PROVIDER: | scopus |
| PUBMED: | 21144756 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 March 2011" - "CODEN: BMECE" - "Source: Scopus" |
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