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

Abstract

Background: Pyrrole compounds having a heterocyclic structure are the most researched and biological activities such as antioxidant and anticancer. 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 B3LYP/DFT method. Pharmacokinetic studies of PhTAD-substituted heterocyclic compounds (I-XIV) were analyzed to show Lipinski's rules via in-silico methods of Swiss-ADME. The drug likeness calculations were carried out Molinspiration analyses. The 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 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 a biologically active compound and is notable for anti-cancer researches.

Synthesis, design, biological evaluation, and computational analysis of some novel uracil-azole derivatives as cytotoxic agents

“…The oral bioavailability and drug-likeness of the synthesized compounds were predicted by using the SwissADME online program [ 41 ]. The results shown in Table 4 proved that the considered derivatives obey Rule of 5 Lipinski.…”

Cytotoxic Potential of Alternaria tenuissima AUMC14342 Mycoendophyte Extract: A Study Combined with LC-MS/MS Metabolic Profiling and Molecular Docking Simulation

“…The Molinspiration web server was used to determine the molecular properties [ 45 , 46 ], and the SwissADME website server was employed to calculate the drug-likeness, ADME, and pharmacokinetic parameters of the identified metabolites [ 33 , 42 ].…”

Design, synthesis, and mechanism study of novel 1-arylisoquinoline derivatives as antifungal agents

“…Molinspiration was used to calculate the main physical and chemical of the target compounds, such as the relative molecular weight, LogP (octanol/water partition coe cient), number of hydrogen bond donors and acceptors, and number of rotatable bonds [30]. ADMET lap was used to calculate the drug-likeness of the target compounds [31].…”