synthesis and cytotoxicity study of new cyclopenta[b] quinoline-1,8-dione derivatives

نویسندگان

ramin miri medicinal and natural products chemistry research center, shiraz university of medical sciences. shiraz, iran. pharmaceutical sciences research center, tehran university of medical sciences. tehran, 14174, iran

omidreza firuzi medicinal and natural products chemistry research center, shiraz university of medical sciences. shiraz, iran.

payam peymani medicinal and natural products chemistry research center, shiraz university of medical sciences. shiraz, iran.

zohreh nazarian pharmaceutical sciences research center, tehran university of medical sciences. tehran, 14174, iran. department of medicinal chemistry, faculty of pharmacy, tehran university of medical sciences, tehran, iran.

چکیده

dna intercalators belong to aromatic heterocyclic compounds interacting reversibly with dna. these compounds have been used extremely as cytotoxic agents against cancer. in this study, the synthesis and biological activity of some novel derivatives of cyclopenta [b] quinoline-1, 8-dione as new intercalating agent were investigated. twenty novel derivatives of cyclopenta [b] quinoline-1, 8-dione were synthesized by molecular condensation of equivalent amount of 3-imino cyclopentanone, corresponding aldehyde and cyclohexane-1, 3-dione. then, their cytotoxic activity was evaluated against hela, ls180, mcf-7 and raji cancer cell lines by mtt assay. the results of cytotoxic activity evaluation indicate that the most of synthesized compounds show weak cytotoxic effect on the different cell lines (ic50 of these compounds is higher than 50 or 100 m ). according to previous studies, in the case of compounds with the weak biological activity, it is more suitable to use ic15 and ic30 instead of ic50 as the indicator of biological activity. since most of compounds have weak cytotoxic effect, we also calculated ic15 and ic30 for evaluating the cytotoxic activity of synthesized compounds. the most potent compound, 6 h (9-(3-bromo-phenyl)-4-pheny l-2, 3, 5, 6, 7, 9-hexahydro-4h-cyclopenta [b] quinoline-1, 8-dione), containing bromophenyl moiety and phenyl substitute on nitrogen of central quinoline ring, show significant cytotoxic activity especially in raji and hela cell lines (ic30: 82 and 24.4 m m respectively) comparing to other compounds. although the results of cytotoxic activity evaluation demonstrated that the in-vitro anti-cancer effect of synthesized compounds are mainly low, it seems that this structure can be used as a novel cytotoxic scaffold for further modification and design of novel potent compounds.

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Synthesis and Cytotoxicity Study of New Cyclopenta[b] quinoline-1,8-dione Derivatives

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عنوان ژورنال:
iranian journal of pharmaceutical research

جلد ۲۰۱۱، شماره ۹، صفحات ۴۸۹-۴۹۶

کلمات کلیدی
[ ' c y t o t o x i c i t y ' , ' c y c l o p e n t a [ b ] q u i n o l i n e ' , 1 , 8 , ' d i o n e ' , ' m t t a s s a y ' , ' d n a ' ]

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