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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*, Syed Riaz Hashim, Priyanka Rani, Sushil Kumar, Navratan Shrimal, Divya Shastri and Vinit Raj   Pages 1 - 13 ( 13 )

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.

Keywords:

4H-Chromene, Molecular Docking, Synthesis, HT-29 Cells, Anticonvulsant Activity

Affiliation:

Department of Chemistry, School of Pharmaceutical Sciences, IFTM University, Moradabad, Uttar Pradesh, Department of Chemistry, School of Pharmaceutical Sciences, IFTM University, Moradabad, Uttar Pradesh, Department of Chemistry, School of Pharmaceutical Sciences, IFTM University, Moradabad, Uttar Pradesh, School of Pharmaceutical Sciences, IFTM University, Moradabad, Uttar Pradesh, Gyan Vihar School of Pharmacy, Suresh Gyan vihar University, Jaipur, Rajasthan, Department of Pharmacy, Central University of Rajasthan, Ajmer, Rajasthan, Gyan Vihar School of Pharmacy, Suresh Gyan vihar University, Jaipur, Rajasthan



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