Design and Synthesis of Novel Heterocyclic-Based 4H-benzo[h]chromene Moieties: Targeting Antitumor Caspase 3/7 Activities and Cell Cycle Analysis.

Fawzia Alblewi,Hany Mohamed,Areej Eskandrani,Rawda Okasha,Ahmed Halawa,Ahmed Mora,Al-Anood Al-Dies,Ahmed El-Agrody,Ahmed Fouda,Tarek Afifi

doi:10.3390/molecules24061060

Abstract

Novel fused chromenes (4,7–11) and pyrimidines (12–16) were designed, synthesized, and evaluated for their mammary gland breast cancer (MCF-7), human colon cancer (HCT-116), and liver cancer (HepG-2) activities. The structural identity of the synthesized compounds was established according to their spectroscopic analysis, such as FT-IR, NMR, and mass spectroscopy. The preliminary results of the bioassay disclosed that some of the target compounds were proven to have a significant antiproliferative effect against the three cell lines, as compared to Doxorubicin, Vinblastine, and Colchicine, used as reference drugs. Particularly, compounds 7 and 14 exerted promising anticancer activity towards all cell lines and were chosen for further studies, such as cell cycle analysis, cell apoptosis, caspase 3/7 activity, DNA fragmentation, cell invasion, and migration. We found that these potent cytotoxic compounds induced cell cycle arrest at the S and G2/M phases, prompting apoptosis. Furthermore, these compounds significantly inhibit the invasion and migration of the different tested cancer cells. The structure-activity relationship (SAR) survey highlights that the antitumor activity of the desired compounds was affected by the hydrophobic or hydrophilic nature of the substituent at different positions.

Highlights

Fused chromenes and benzochromenes are notoriously established molecules that exhibit miscellaneous biological activities, such as antibacterial and antifungal activity [1,2,3], being an anticancer agent [4], blood platelet antiaggregating [5], hypolipidemic [6], antioxidant [7,8], antileishmanial [9], vascular-disrupting [10], anticancer, spectroscopic properties, and fluorescence [11,12] activities and effects
Thelines, 2-N-succinimido derivatives (B)mitosis display an antieffective antiproliferative vehicle for different causing a hindrance to the phase and behaviors against different cellβ-enaminonitriles lines: MCF-7, MDA-MB-231, HepG-2, T-47D,cytotoxic
Our results revealed that the prepared compounds trigger cancer cell arrest in fragmentation

Summary

Introduction

Fused chromenes and benzochromenes are notoriously established molecules that exhibit miscellaneous biological activities, such as antibacterial and antifungal activity [1,2,3], being an anticancer agent [4], blood platelet antiaggregating [5], hypolipidemic [6], antioxidant [7,8], antileishmanial [9], vascular-disrupting [10], anticancer, spectroscopic properties, and fluorescence [11,12] activities and effects. Is an effective antiproliferative vehicle for different cell lines, causing a hindrance to the (LY290181). Is an effective antiproliferative vehicle for different cell lines, causing a hindrance to rheumatic effect [15], while β-enaminonitriles (C) [16]. Have effective cytotoxic and apoptotic the mitosis phase and microtubules [13,14]. (B)mitosis display an antieffective antiproliferative vehicle for different causing a hindrance to the phase and behaviors against different cellβ-enaminonitriles lines: MCF-7, MDA-MB-231, HepG-2, T-47D,cytotoxic

Methods

Results

Conclusion