Abstract |
A novel class of molecules with structure N-[3-(4-substituted-1-piperazinyl) propyl]-6-methoxy naphthalene-2-carboxamides were designed by generating a pharmacophore for potent MDR reversal activity, using Elacridar ( GF 120918) as a query molecule and using MOE software. They were synthesized by condensing 6-methoxynaphthalene-2-carboxylic acid with N-[3-(4-substituted-1-piperazinyl) propyl] amines in the presence of DCC in DMF. They were evaluated in P388 murine lymphocytic leukemia cell line (P388) in vitro using SRB assay for cytotoxicity and in adriamycin-resistant P388 murine lymphocytic leukemia cell line (P388/ADR) using MTT assay for resistant reversal activity. Test compounds were non-toxic at the doses studied (upto 80 microg/ml). They effectively reversed adriamycin resistance at the doses studied (40 and 80 microg/ml). The percentage enhancement in adriamycin activity was in the range 33.58 -90.67 (at 40 microg/ml) and 8.80-46.04 (at 80 microg/ml) and the corresponding reversal potency values were in the range 1.33-1.90 and 1.08-1.46, respectively. Test compounds 2, 3, and 5 exhibited better activity as compared to the standard resistant reversal agent ( Verapamil), at same concentration.
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Authors | Tushar N Lokhande, C L Viswanathan, Advait Joshi, Aarti Juvekar |
Journal | Bioorganic & medicinal chemistry
(Bioorg Med Chem)
Vol. 14
Issue 17
Pg. 6022-6
(Sep 01 2006)
ISSN: 0968-0896 [Print] England |
PMID | 16730993
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amides
- Antineoplastic Agents
- Naphthalenes
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Topics |
- Amides
(chemical synthesis, chemistry, pharmacology)
- Animals
- Antineoplastic Agents
(chemistry, pharmacology)
- Cell Line, Tumor
- Drug Design
- Drug Resistance, Neoplasm
(drug effects)
- Leukemia P388
- Mice
- Molecular Structure
- Naphthalenes
(chemical synthesis, chemistry, pharmacology)
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