Pharmacological Evaluation of Aldehydic-Pyrrolidinedione Against HCT-116, MDA-MB231, NIH/3T3, MCF-7 Cancer Cell Lines, Antioxidant and Enzyme Inhibition Studies

Abstract

Purpose

The current work was designed to synthesize a bioactive derivative of succinimide and evaluate it for anti-Alzheimer, anticancer and anti-diabetic potentials.

Methods

The compound was synthesized by Michael addition of butyraldehyde with N-phenylmaleimide. The synthesized compound was screened for biological potentials including anti-cholinesterase, in-vitro anti-diabetic, antioxidant and anthelmintic potentials. The anti-cholinesterase potential was evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), anti-diabetic potential against α-glucosidase, antioxidant potential against ABTS, DPPH and H₂O₂ and anthelmintic potential against Perethima posthuma and Ascaridia galli respectively.

Results

The compound demonstrated significant AChE and BChE inhibition i.e., 71.34±1.92 and 73.42 ±1.92 at the concentration of 1000 µg/mL respectively. Other dilutions exhibited concentration-dependent inhibitory activity against both enzymes. In the MTT assay, the newly synthesized compound was found active against all of the cell lines viz, HCT-116, MDA-MB231, NIH/3T3 and MCF-7 and the highest cytotoxicity potential was observed against the colon cancer cell line (HCT-116) with an IC₅₀ value of 78 µg/mL exhibiting its highest potential. Moreover, the compound exhibited prominent α-glucosidase inhibitory potentials (79.86±2.54% at 1000 µg/mL) with IC₅₀ value of 156.23 µg/mL. Further, our test compound exhibited considerable scavenging activity against DPPH, ABTS and H₂O₂ free radicals with percent inhibitions of 75.84±1.58, 72.85±1.17 and 54.82±1.82 and IC₅₀ values of 84.36, 139.74 and 752.21 µg/mL respectively. Our test sample exhibited significant anthelmintic potentials. It demonstrated significant paralysis and death of the test worms in an unbelievably short time in comparison with albendazole.

Conclusion

Going into the detail of all observations, it may be deduced that the newly synthesized succinimide derivative could be an important drug candidate against neurodegenerative disorders like Alzheimer’s disease, cancer, diabetes mellitus and worms. Further detailed studies in animal models are required for in-vivo analysis of the compound.

Keywords:

• Succinimide
• Alzheimer’s disease
• MTT
• oxidative stress
• diabetes
• helminthiasis

Acknowledgments

We are grateful to Department of Pharmacy, University of Malakand, Chakdara, Khyber Pakhtunkhwa, Pakistan for provision of facilities to complete this project. The authors also extend their appreciation to Researchers Supporting Project Number (RSP-2019/110), King Saud University Riyadh Saudi Arabia for funding support.

Disclosure

The authors report no conflicts of interest in this work.