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Papers of the Week

Papers: 26 Aug 2023 - 1 Sep 2023

Basic Science

In Silico Studies, In Vitro Studies, Molecular/Cellular, Pharmacology/Drug Development


2023 Aug 04

Bioorg Chem



Blocking the major inflammatory pathways by newly synthesized thiadiazine derivatives via in-vivo, in-vitro and in-silico mechanism.


Habib Ullah S, Khan A, Ahsan Halim S, Khan R, Pan XD, Ullah R, Wadood A, Khalid A, Abdalla AN, Khogeer S, Al-Harrasi A


A series of new thiadiazine derivatives including 2-(5-alkyl/aryl-6-thioxo-1,3,5-thiadiazinan-3-yl) propanoic acids (a) and 4-methyl-2-(5-alkyl/aryl-6-thioxo-1,3,5-thiadiazinan-3-yl) pentanoic acids (b) were synthesized by reacting primary alkyl/aryl amines with CS, followed by reaction with formaldehyde and amino acids. The chemical structures of synthesized compounds were confirmed by C- NMR and H- NMR techniques. The inhibitory potential of major inflammatory enzymes, COX-2 and 5-LOX was examined. Moreover, anti-nociceptive and anti-inflammatory activities were evaluated in the in vivo thermally induced nociceptive, and carrageenan induced paw edema models in mice. The in-vitro results reflect that these compounds exhibited concentration dependent inhibition of COX-2 and 5-LOX. The tested compounds at 50 mg/kg showed significant effect on thermally induced pain, and reduced latency time (seconds) as compared to the vehicle treated animals. Moreover, tested compounds exhibited percent inhibition of paw edema in the carrageenan induced paw edema model in mice. Furthermore, the binding modes of the most active COX-2 and 5-LOX inhibitors were determined through computational methods. The computational study reflects that the docked compounds have high binding affinities for COX-2 and 5-LOX enzymes, which leads to inhibition of these enzymes.