title: Novel 2,4-dichlorophenoxy acetic acid substituted thiazolidin-4-ones as anti-inflammatory agents: Design, synthesis and biological screening.
abstract: A library of fourteen 2-imino-4-thiazolidinone derivatives (1a-1n) has been synthesized and evaluated for in vivo anti-inflammatory activity and effect on ex-vivo COX-2 and TNF-α expression. Compounds 1k (5-(2,4-dichloro-phenooxy)-acetic acid (3-benzyl-4-oxo-thiazolidin-2-ylidene)-hydrazide) and 1m (5-(2,4-dichloro-phenooxy)-acetic acid (3-cyclohexyl-4-oxo-thiazolidin-2-ylidene)-hydrazide) exhibited in vivo inhibition of 81.14% and 78.80% respectively after 5h in comparison to indomethacin which showed 76.36% inhibition of inflammation without causing any damage to the stomach. Compound 1k showed a reduction of 68.32% in the level of COX-2 as compared to the indomethacin which exhibited 66.23% inhibition of COX-2. The selectivity index of compound 1k was found to be 29.00 in comparison to indomethacin showing selectivity index of 0.476. Compounds 1k and 1m were also found to significantly suppress TNF-α concentration to 70.10% and 68.43% in comparison to indomethacin which exhibited 66.45% suppression.
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Yakub
authors.initials: Y
authors.lastname: Ali
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India. Electronic address: msalam@jamiahamdard.ac.in.
authors.forename: Mohammad Sarwar
authors.initials: MS
authors.lastname: Alam
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India. Electronic address: hhamid@jamiahamdard.ac.in.
authors.forename: Hinna
authors.initials: H
authors.lastname: Hamid
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Asif
authors.initials: A
authors.lastname: Husain
authors.affiliation: CSIR Unit for Research and Development of Information Products, Pune 411038, India.
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Dhulap
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Sameena
authors.initials: S
authors.lastname: Bano
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Chetna
authors.initials: C
authors.lastname: Kharbanda
mesh_terms: D015084:2,4-Dichlorophenoxyacetic Acid / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000517:prevention & control; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D015084:2,4-Dichlorophenoxyacetic Acid
keywords: 2-Imino-4-thiazolidinone; Anti-inflammatory; Anti-nociceptive; COX-2; TNF-α; Ulcerogenic