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Current Computer-Aided Drug Design


ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

Research Article

Antioxidant, Cytotoxic Activity and Pharmacokinetic Studies by Swiss Adme, Molinspiration, Osiris and DFT of PhTAD-substituted Dihydropyrrole Derivatives

Author(s): Arif Ayar*, Masuk Aksahin, Seda Mesci, Burak Yazgan, Melek Gül and Tuba Yıldırım

Volume 18, Issue 1, 2022

Published on: 23 February, 2021

Page: [52 - 63] Pages: 12

DOI: 10.2174/1573409917666210223105722


Background: Pyrrole compounds having a heterocyclic structure are the most researched and biological activities such as antioxidant and anticancer activities.

Objective: Herein is a first effort to study the significance of heterocyclic compounds to include pyrrole and triazolidine-3,5-dion moiety, on the pharmacokinetic, antioxidant activity and cytotoxic activity on MCF-7 and MCF-12A cell lines.

Method: The molecular structures of compounds I-XIV were simulated by the theoretical B3- LYP/DFT method. Pharmacokinetic studies of PhTAD-substituted heterocyclic compounds (IXIV) were analyzed to show Lipinski's rules via in-silico methods of Swiss-ADME. The drug likeness calculations were carried out in Molinspiration analyses. Some toxicity risk parameter can be quantified using Osiris. Antioxidant activities determined by DPPH, Fe+2 ions chelating and reducing. Cytotoxic activity measured by MTT and RTCA

Results: Compared with the DPPH activity, the metal chelating activity exhibited serious similar antioxidant effects by PhTAD substituted pyrrole compounds. The same compounds showed the highest activity among the two antioxidant activities. The IC50 values of the compounds are in the range of 12 and 290 μM in the MCF-7 cell line. In the MTT and RTCA assays, All compounds showed cytotoxic activity, but about half of the fourteen compounds showed high cytotoxicity. IC50 values of the compounds are in the range of 5 and 54 μM for MTT and range of 1.5 and 44 μM for RTCA.

Conclusion: Data of the antioxidant and cytotoxic activity of PhTAD-substituted dihydropyrrole- derived compounds in MCF-7 and MCF-12A cell lines confirmed that the compounds are biologically active compound and are notable for anti-cancer researches.

Keywords: Breast cancer, PhTAD-Dihydropyrrole, antioxidant activity, RTCA, swiss-ADME, molinspiration, osiris.

Graphical Abstract
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