Anti-Inflammatory, Radical Scavenging Mechanism of New 4-Aryl-[1,3]-thiazol-2-yl-2-quinoline Carbohydrazides and Quinolinyl[1,3]-thiazolo[3,2-b][1,2,4]triazoles

Graphical Abstract

As evidenced by the molecules 5 c and 7 c showing good interaction (hydrogen bonds and short interactions) with protein trypsin. The trypsin residues Phe⁴¹, Lys⁶⁰, Gly¹⁹³, Ser¹⁹⁵, Gly¹⁹³, Ser¹⁹⁵, Lys⁶⁰ and Phe⁴¹ interacts with compound 7 c. Similarly, compound 5 c interacts with the residues Lys⁶⁰, His⁵⁷, Gln¹⁹², Gly¹⁹³, Ser¹⁹⁵, Lys⁶⁰, His⁵⁷, Ser¹⁹⁵, Gln¹⁹² and Gly¹⁹³. The newly synthesized compounds are highly potent inhibitors of Trypsin thus providing new scope in drug discovery.

Abstract

Quinolines, thiazole and many thiazolotriazoles have been given insistence because of diversification in medicinal and biological properties associated with them. In view of these observations, it is therefore proposed to synthesize and study the biological properties of some novel quinolinylthiazolotriazole derivatives. All derivatives were characterized by FTIR, ¹H NMR, ¹³C NMR and mass spectra. All compounds 5 a–g and 7 a–g series were screened for antioxidant and anti-inflammatory potential. In 5 a-g series, compounds 5 c (4-NO₂) and 5 a (4-Br) derivatives showed free radical scavenging activity with IC₅₀ values of 425.9 μg/ml and 413.3 μg/ml. In 7 a-g series, compound 7 c (3-NO₂) and 7 g (4-OH) derivatives showed highest free radical scavenging activity with IC₅₀ values 7.75 μg/ml and 14.06 μg/ml. Compounds 5 a, 5 c, 7 c and 7 g exhibited pronounced anti-inflammatory activity among all other synthesized compounds. Molecular docking studies revealed good binding through hydrogen bonding with catalytic residues as well as neighboring residues at the active site of target protein trypsin. Among all the synthesized compounds 5 c, 5 a, 7 c and 7 g showed least binding energy values of −10.70 kcal/mol, −9.69 kcal/mol, −11.47 kcal/mol and −9.83 kcal/mol respectively. Results from antioxidant, anti-inflammatory and in silico studies suggest that the synthesized compounds may be potential antioxidant and anti-inflammatory agents and can act as lead molecules in drug discovery.