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

Ashfaq Ahmad,1 Farhat Ullah,1 Abdul Sadiq,1 Muhammad Ayaz,1 Haroon Rahim,2 Umer Rashid,3 Sajjad Ahmad,1 Muhammad Saeed Jan,1 Riaz Ullah,4 Abdelaat A Shahat,4,5 Hafiz Majid Mahmood6 1Department of Pharmacy, University of Malakand, Chakdara, Dir (L), KP (Khyber Pakhtunkhwa) 18000, Pakistan; 2Department of Pharmacy, Sarhad University of Science & Information Technology, Peshawar, KP (Khyber Pakhtunkhwa), Pakistan; 3Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, KP (Khyber Pakhtunkhwa), Pakistan; 4Department of Pharmacognosy (MAPPRC), College of Pharmacy, King Saud University Riyadh, Riyadh, Saudi Arabia; 5Phytochemistry Department, National Research Centre, Giza, Egypt; 6Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaCorrespondence: Haroon Rahim; Abdul SadiqDepartment of Pharmacy, Sarhad University of Science and Information Technology Peshawar, Peshawar, Khyber Pakhtunkhwa, Pakistan; Department of Pharmacy, University of Malakand Khyber Pakhtunkhwa, Chakdara 18800, PakistanTel +92-3329461642; +92-301-2297102Email hrahimpk@gmail.com, sadiquom@yahoo.comPurpose: 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