Title:Synthesis of Novel Aryl (4-Aryl-1H-Pyrrol-3-yl) (Thiophen-2-yl) Methanone Derivatives: Molecular Modelling, In Silico ADMET, Anti-Inflammatory and Anti-Ulcer Activities
Volume: 20
Issue: 2
Author(s): Arif Pasha*, Sumanta Mondal and Naresh Panigrahi
Affiliation:
- Department of Pharmaceutical Chemistry, GITAM Institute of Pharmacy, Rushikonda, GITAM (Deemed to be University), Visakhapatnam, Andhra Pradesh, 530045,India
Keywords:
Chalcones, TosMIC, pyrrole, anti-inflammatory, anti-ulcer activities, derivatives.
Abstract:
Background: Due to the presence of both five-membered heterocyclics like pyrrole and
thiophene in one molecule considerable attention was made for their enormous pharmacological activities
out of which include anti-inflammatory and anti-ulcer activities.
Objective: Chalcones with toluenesulfonylmethyl isocyanide (TosMIC) undergo synthesis to form
some new aryl (4-aryl-1H-pyrrol-3-yl) (thiophen-2-yl) methanone derivatives. Molecular docking
of synthesized compounds with protein receptors of anti-inflammatory COX-1(3N8Y), COX-2
(1PXX) along with anti-ulcer H+/K+ATPase enzyme (2XZB) followed with drug-likeness, and in
silico ADMET properties.
Materials and Methods: The multicomponent reaction was carried out by the intermediate formation
of α, β-unsaturated ketone from carbonyl compounds which on sequential addition undergoes
[3+2] cycloaddition reaction in same medium affords aryl (4-aryl-1H-pyrrol-3-yl) (thiophen-2-yl)
methanone derivatives by addition of TosMIC in basic medium had resulted in series of compounds
PY1 to PY12. All the new synthesized compounds were screened for their in-vitro anti-inflammatory
activity by bovine serum albumin method followe with COX assay, and in-vivo by using
carrageenan-induced rat paw edema method of the selected compounds PY1, PY5 and PY12
which is also screened for anti-ulcer activity by pylorus ligation method, respectively. Molecular
docking was performed using autodock tools, drug-likeness by OSIRIS property explorer and admetSAR
properties.
Results and Discussion: From the synthesized compounds of aryl (4-aryl-1H-pyrrol-3-yl) (thiophen-
2-yl) methanone derivatives PY5 showed decent in-vitro and in-vivo anti-inflammatory along
selectivity index of 6.2 for COX-1 with IC50(μM) value of 9.54 over diclofenac with 8.74 and
PY1 showed decent in-vivo anti-ulcer activities along with drug-likeness and in silico ADMET predictions
revealed that all the synthesized compounds have minimal toxic effects with good absorption
as well as solubility characteristics. The selected compounds may serve as potential lead compounds
for developing new anti-inflammatory and anti-ulcer drugs.
Conclusion: From the newly synthesized molecules PY5 was found to be effective for anti-inflammatory
and PY1 was found to be effective for anti-ulcer activities further derivitization and designed
of modification to achieve more compounds with potent anti-inflammatory and anti-ulcer activities.
