Future medicinal chemistry · 2025
Development of novel furan-based VEGFR-2 inhibitors and apoptotic inducers for colorectal cancer.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Elkaeed Eslam B, Al Ward Maged Mohammed Saleh, Elkady Hazem, Yousef Reda G, Elsheshiny Asmaa A A, Abdelfattah Shimaa S, El-Fakharany Esmail M, Alsfouk Aisha A, Metwaly Ahmed M, Eissa Ibrahim H
Аннотация
AIMS: This study aimed to synthesize and evaluate novel furan derivatives as potential anticancer agents targeting colon cancer through VEGFR-2 inhibition and apoptosis induction.
MATERIALS AND METHODS: The cytotoxic activity of the synthesized compounds was assessed against human fibroblast (HSF) and colon cancer cell lines (HCT-116, Caco-2, and HT-29) using the MTT assay. VEGFR-2 inhibitory activity was determined in vitro, and immunocytochemistry was employed to evaluate VEGFR-2 expression. Apoptosis, cell cycle arrest, and migration inhibition were analyzed in Caco-2 cells. Molecular docking, molecular dynamics (MD) simulations, Density Functional Theory (DFT), and ADMET analyses were conducted to assess binding affinity, stability, and safety profiles.
RESULTS: Compound 6 exhibited potent cytotoxicity against HT-29 (IC50 = 22.39 μM) and strong VEGFR-2 inhibition (IC50 = 0.28 ± 0.42 μM), comparable to sorafenib. It suppressed VEGFR-2 expression, induced G2/M cell cycle arrest, and promoted early and late apoptosis in 97% of treated Caco-2 cells. Upregulation of Bax and caspase-3, along with downregulation of Bcl-2, confirmed intrinsic apoptotic activation. Computational analyses supported compound 6's stability and drug-likeness.
CONCLUSIONS: Compound 6 is a promising lead furan derivative with potent, selective anticancer activity against colon cancer via VEGFR-2 inhibition and apoptosis induction. Further, in vivo evaluation is warranted.
MATERIALS AND METHODS: The cytotoxic activity of the synthesized compounds was assessed against human fibroblast (HSF) and colon cancer cell lines (HCT-116, Caco-2, and HT-29) using the MTT assay. VEGFR-2 inhibitory activity was determined in vitro, and immunocytochemistry was employed to evaluate VEGFR-2 expression. Apoptosis, cell cycle arrest, and migration inhibition were analyzed in Caco-2 cells. Molecular docking, molecular dynamics (MD) simulations, Density Functional Theory (DFT), and ADMET analyses were conducted to assess binding affinity, stability, and safety profiles.
RESULTS: Compound 6 exhibited potent cytotoxicity against HT-29 (IC50 = 22.39 μM) and strong VEGFR-2 inhibition (IC50 = 0.28 ± 0.42 μM), comparable to sorafenib. It suppressed VEGFR-2 expression, induced G2/M cell cycle arrest, and promoted early and late apoptosis in 97% of treated Caco-2 cells. Upregulation of Bax and caspase-3, along with downregulation of Bcl-2, confirmed intrinsic apoptotic activation. Computational analyses supported compound 6's stability and drug-likeness.
CONCLUSIONS: Compound 6 is a promising lead furan derivative with potent, selective anticancer activity against colon cancer via VEGFR-2 inhibition and apoptosis induction. Further, in vivo evaluation is warranted.