ارزيابي اثر سميت پيريدوپيريميدين‌هاي سنتزي استخلاف‌دار شده بر روي رده‌‌هاي سلولي نرمال و سرطاني

Evaluation of cytotoxicity effect of Synthetic Pyridopyrimidine derivatives on the cancer vs. normal cell lines

مطالعه­ هاي اخير در دو مدل آزمايشگاهي و حيواني نشان مي­دهد،كه مشتق­ هاي پيريدوپيريميدين داراي اثرگذاري مؤثر بر بيماري­هاي مزمن از جمله سرطان است، هدف از اين مطالعه سنتز چهار مشتق پيريدوپيريميدين و ارزيابي آثر آن­ها بر سل لاين­هاي سرطاني و نرمال است. مواد و روش: پس از كشت رده‌هاي سلولي مختلف سرطاني MCF-7،MAD-MB-231،-4 MOLT و PC-3 و نرمالHFF در پليت­هاي 96 خانه، سلول‌ها با چهار غلظت‌ 1000،500،50،5 نانومولار در بازه‌هاي زماني 72،48،24 ساعت، با پيريدوپيرميدين­هاي سنتزي جهت بررسي اثرگذاري اين مواد با تست سميت (MTT assay) تيمار گرديد، آناليزهاي آماري داده‌ها با نرم‌افزار SPSS16 با دو آزمون واريانس يك‌طرفه و متعاقب آن تست توكي در سطح 05/0 >P value گزارش گرديد. يافته‌ها: نتايج اين پژوهش نشان داد كه تركيب‌هاي پيريدوپيرميدين در غلظت هاي مشخص اثر سميت معني­داري بر روي رده سلول‌هاي نرمال نداشتند، اما بررسي اثر آن بر روي رده‌هاي سلولي سرطاني در سطح 05/0 >P value نشان داد كه مهار رشد سلولي با افزايش غلظت و زمان افزايش پيدا مي‌كند، همچنين نتايج نشان داد پيريدوپيرميدين­هاي داراي گروه­هاي برومايد در غلظت 500 الي 1000 نانومولار در بازه زماني 72 ساعت تأثير مؤثرتري بر مهار رشد سلول‌هاي سرطاني نشان دادند. نتيجه‌گيري: نتايج به‌دست‌آمده از اين پژوهش اثر پيريميدين­ها را بر روي رده­ هاي سلولي سرطاني نشان داد و استفاده از اين تركيب‌ها به‌عنوان گزينه جذاب براي مقابله با بيماري‌هاي مزمن در جهان به‌صورت داروهاي جايگزين يا تركيب با داروهاي معمول را پيشنهاد مي‌كند.

Recently, studies have been reported in vitro and in vivo, that these pyridopyrimidine compounds have a beneficial effect on chronic diseases such as cancer. this study was designed to evaluate the effects of synthetic pyridopyrimidine compounds on the growth and proliferation of normal and cancer cell lines. Material and Methods: Cytotoxic effect of synthetic pyridopyrimidine at different concentrations and period on the MCF-7, MAD-MB-231, MOLT-4, PC-3, and Normal Fibroblast (HFF) cell lines were cultured in 96-well plates, thin cells were treated with synthetic compounds at different concentrations 1000, 500, 50, 5 nM at 24,48 and 72 hours, to evaluate the effect using MTT assay. the resulting data were analyzed using SPSS16 software with one-way ANOVA followed by the Tukey test and P <0.05 was considered as a significant difference. Results: The results of this study showed that pyridopyrimidine compounds had no significant toxicity effect on the normal cell lines, Nevertheless showed strong and dose-dependent inhibition of cancer cell growth at P-value <0.05. also, results showed that pyridopyrimidines with bromide groups at a concentration of 500 to 1000 nM had a more effective effect on inhibition of cancer cell growth inhibition at 72 hours. Conclusion: Results of this study indicated the pyrimidines inhibition effect on cancer cell lines, however, the use of these compounds as an attractive option in chronic diseases treatment in the world as alternative medicines or combination with conventional medicines are suggested Keywords: Pyridopyrimidines,Normal and Cancer Cell lines, MTT assay, IC50Aim and Background: Recently, studies have been reported in vitro and in vivo, that these pyridopyrimidine compounds have a beneficial effect on chronic diseases such as cancer. this study was designed to evaluate the effects of synthetic pyridopyrimidine compounds on the growth and proliferation of normal and cancer cell lines. Material and Methods: Cytotoxic effect of synthetic pyridopyrimidine at different concentrations and period on the MCF-7, MAD-MB-231, MOLT-4, PC-3, and Normal Fibroblast (HFF) cell lines were cultured in 96-well plates, thin cells were treated with synthetic compounds at different concentrations 1000, 500, 50, 5 nM at 24,48 and 72 hours, to evaluate the effect using MTT assay. the resulting data were analyzed using SPSS16 software with one-way ANOVA followed by the Tukey test and P <0.05 was considered as a significant difference. Results: The results of this study showed that pyridopyrimidine compounds had no significant toxicity effect on the normal cell lines, Nevertheless showed strong and dose-dependent inhibition of cancer cell growth at P-value <0.05. also, results showed that pyridopyrimidines with bromide groups at a concentration of 500 to 1000 nM had a more effective effect on inhibition of cancer cell growth inhibition at 72 hours. Conclusion: Results of this study indicated the pyrimidines inhibition effect on cancer cell lines, however, the use of these compounds as an attractive option in chronic diseases treatment in the world as alternative medicines or combination with conventional medicines are suggested