Abas, Mujahid; Nazir, Yasir; Ashraf, Zaman; Iqbal, Zafar; Raza, Hussain; Hassan, Mubashir; Jabeen, Erum; Bais, Abdul published the artcile< A Practical Method of N-Methyl-pyrrole Disulfonamides Synthesis: Computational Studies, Carbonic Anhydrase Inhibition and Electrochemical DNA Binding Investigations>, HPLC of Formula: 3731-53-1, the main research area is methylpyrrole disulfonamide preparation carbonic anhydrase inhibitor antitumor SAR cytotoxicity; mol docking DNA binding.
A series of N-methylpyrrole derivatives bearing disulfonamide functional group, I [R = Bu, Ph, 4-pyridyl, etc.] were synthesized by following a simple nucleophilic substitution reaction route to explore their carbonic anhydrase inhibitory activity. N-methylpyrrole was converted into N-methylpyrrole disulfonyl chloride, which upon condensation with various aliphatic and aromatic amines, yielded the final products I. In-silico docking results predicted strong binding of synthesized compounds I in an enzymic pocket of human carbonic anhydrase isoenzyme II (PDB ID 4Q6D). In-vitro carbonic anhydrase inhibitory assays revealed that analogs I [R = Bu, 2-pyridylethyl] were most potent with IC50 0.38±0.01μM and 0.75±0.88μM resp. in comparison to standard acetazolamide (IC50 0.99±0.04μM). The enzyme inhibitory kinetics exhibited I [R = 2-pyridylethyl] a noncompetitive inhibitor with Km and Ki values as 0.34 mM and 18.2μM resp. The compounds I [R = Bu, 2-pyridylethyl] showed very little cytotoxicity against human keratinocyte (HaCaT) with 80% cell viability and the anticancer activity performed against MCF-7 cell line showed that the compounds I [R = Bu, 2-pyridylethyl] caused 80% and 45% cell death resp. at 125μM concentrations Combining the results of DNA binding anal. through the UV-Vis spectroscopy (hypochromism), cyclic voltammetry (current decrease), and fluorescence spectroscopy (hypochromism in intercalator’s peak); mixed binding mode (intercalation + groove binding) was suggested for I [R = 2-pyridylethyl] and intercalation for I [R = n-butyl] with stronger DNA binding of I [R = 2-pyridylethyl] than I [R = n-butyl]. Based on our results I [R = Bu, 2-pyridylethyl] may be proposed to serve as a lead structure for designing potentially more active CAIs.
ChemistrySelect published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 3731-53-1 belongs to class pyridine-derivatives, and the molecular formula is C6H8N2, HPLC of Formula: 3731-53-1.