Silica catalyzed one pot synthesis of hybrid thiazolidin-4-one derivatives as anti-tubercular and anti-inflammatory agent by attenuating COX-2 pathway

Abstract

A novel series of a hybrid class of hybrid thiazolidin-4-one derivatives were designed and synthesized through one-pot catalytic synthesis. The reaction was catalyzed in the presence of silica-H₂SO4⁽⁺⁶⁾. The derivatives computational ADMET profile was calculated. The study shows that most active derivatives have optimal logP, higher anti-inflammatory activity score, and poor metabolism at the sight of P450-3A4 and 2D6. The entire series of derivatives were further evaluated for anti-tubercular (against Mycobacterium tuberculosis H37Rv (Resistant strain)) and anti-inflammatory activity (in-vivo assay using Wistar rat). The result showed that derivatives 4c, 4h, and 4m have significant potency against tested M. tuberculosis. However, derivatives 4i and 4j found significantly active against inflammation. In vitro COX inhibition assay also supported the result in favor of selectivity and efficacy of derivatives.

GRAPHICAL ABSTRACT

KEYWORDS:

• ADME
• anti-inflammatory activity
• docking
• thiadiazole
• thiazolidine-4-one

Disclosure statement

The authors have declared that there is no conflict of interest.

Additional information

Funding

The work was supported by Act 211 Government of the Russian Federation, contract 02.A03.21.0011; Ministry of Education and Science of Russia, Grant/Award Numbers: 4.8298.2017/8.9, 4.7279.2017/8.9; Russian Foundation of Basic Research (RFBR), Grant/Award Number: 18‐53‐45018; and SHUATS, Allahabad, India.