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Medicinal Chemistry


ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Research Article

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

Author(s): Divya Chauhan*, Syad Riaz Hashim, Prinka Rani, Sushil Kumar, Navratan Shrimal, Divya Shastri and Vinit Raj*

Volume 17, Issue 3, 2021

Published on: 06 December, 2019

Page: [203 - 215] Pages: 13

DOI: 10.2174/1573406415666191206101617

Price: $65


Background: Privileged 4H-chromenes possess potent anticancer and anticonvulsant activities. By the inspiring potency of 4H-chromenes and demands of the present era of scaffolds, an effective molecule was discovered for the treatment of cancer and related diseases.

Objective: This study designed and synthesized a novel series of 4H-chromene derivatives from one-port synthesis for the treatment of cancer and other such diseases.

Methods: A side amide chain was substituted in multiple steps on the amine group of chromene. Later, the anticancer activity of synthesized compounds was investigated against the human colon adenocarcinoma cell line (HT-29) using sulforhodamine B (SRB) assay. Moreover, anticonvulsant activity was also detected using maximal electroshock seizure (MES) model and subcutaneous Metrazol Seizure Threshold Test (scMET) in albino Wistar rats. Neurotoxicity was evaluated by using the 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.

Results: 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, and 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 for treatement against colon cancer, while compound A9 may be used as a considerable effective molecule for the treatment of epilepsy.

Keywords: Anticonvulsant activity, 4H-Chromene, molecular docking, synthesis, HT-29 cells, epilepsy.

Graphical Abstract
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