Discovery of Substituted N-(6-Chloro-3-cyano-4-phenyl-4H-chromen-2-yl)- 2-(4-chloro-phenoxy)-acetamide for Biphasic Anticancer and Anticonvulsant Activities

Abstract

Background : Privileged 4H-chromenes possess the potent anticancer and anticonvulsant actives. By inspiring potency of 4H-chromenes and demands of present era of scaffold, discovery of effective molecule was carried out for the treatment of cancer and conversant. Objective : Designed and synthesized a novel series of 4H-chromene derivatives from one port synthesis for the treatment of cancer and conversant. Method : Substitution of side amide chain was formed in multiple steps on amine group of chromene. Later, anticancer activity of synthesized compounds was investigated against human colon adenocarcinoma cell line (HT-29) using sulforhodamine B (SRB) assay. Moreover, anticonvulsant activity was also screened out by using maximal electroshock seizure (MES) model and subcutaneous Metrazol Seizure Threshold Test (scMET) in albino Wistar rats. Neurotoxicity was evaluated using by rotarod test. Before the synthesis, docking studies were performed using various molecular targets. Subsequently, the computational study of the titled compounds was performed to predict the pharmacokinetic profile. Result: Among the fifteen tested compounds, A4 and A9 were found to be active against HT-29 cells (growth inhibitory dose 50% (GI50) <11µM). Moreover, compounds A4 showed the protection at 300mg/kg in scMET (h) for albino Wistar rats and compounds A9, A11, A15 exhibited the anticonvulsant effect at the doses 100, 300 and 300 mg/kg, respectively in MES screen(h). Conclusion : Due to these encouraging results, we concluded that both A4 and A9 may be effective against colon cancer. While compound A9 may be used as a considerable effective molecule for the treatment of epilepsy.

Silica nanospheres KCC-1 as a good catalyst for the preparation of 2-amino-4H-chromenes by ultrasonic irradiation

“…Also compounds 4 and 5 showed in Fig. 1 the maximum inhibitory effect against the HT29 human colon cancer cells 10 . Chromenes have been used for the treatment of different diseases of connective tissues, diabetes, psoriasis, pernicious anemia, ulcerous colitis, and chronic hepatitis 11 .…”

2H/4H-Chromenes—A Versatile Biologically Attractive Scaffold

“…On the other hand, both studies strongly correlated and supported the author's hypothesis. Therefore, these compounds might have better potency to bind with the cancer protein targets (Chauhan et al, 2020 ).…”

“…Consequently, the substitution of electron-withdrawing groups, for example, p-NO 2 and p-Cl at R and p-Cl and p-Br at the R1 position, led to an improvement in the antiproliferative potency. This means that Br and -Cl atoms have a larger size and lower lipophilicity, which helps cause stronger interactions with the anticancer targets ( Figure 8A ) (Chauhan et al, 2020 ).…”

Docking Studies, Synthesis and Evaluation of Anticancer Activity of 4H-Chromene Derivatives

“…A wide range of new chromene-based natural products were reported during the last two decades. 6 These heterocyclic natural and synthetic benzopyran derivatives possess important biological properties such as anticancer, 7 anti-coagulant, 8 antimicrobial, 9 anti-proliferative, 10 antioxidant, 11 antifungal, 12 antiestrogenic, 13 antiviral, 14 antitubercular, 15 anti-inflammatory 16 and anticonvulsant 17 activities. During recent years, several researchers developed different 4H-chromene derivatives with anti-breast cancer activity through the introduction of various heterocyclic scaffolds (Figure 1).…”