title: Design, synthesis and pharmacological screening of novel antihypertensive agents using hybrid approach.
abstract: Eight derivatives of general formula 2-(2-(4-(3-((5-substituted methylene)-4-oxo-2-(phenylimino)thiazolidin-3-yl)-2-hydroxypropylamino)benzoyl)hydrazinyl)-2-oxoethyl nitrate were synthesized and tested for electrocardiographic, antiarrhythmic, vasorelaxing and antihypertensive activity as well as for in-vitro nitric oxide (NO) releasing ability. Compound 8b 2-(2-(4-(3-(5-benzyliden-4-oxo-2-(phenylimino)thiazolidin-3-yl)-2-hydroxypropylamino)benzoyl)hydrazinyl)-2-oxoethyl nitrate, was the most potent in this series. The pharmacological results suggested that the antiarrhythmic effects of these compounds were related to their adrenolytic properties which are believed to be due to the presence of the 5-(substituted)methylen-2-(phenylimino)thiazolidin-4-one moiety with less bulky, electron donating substituent on the phenyl ring at 5th position of the thiazolidin-4-one. In conclusion, most of the synthesized compounds were significantly potent as antiarrhythmic and antihypertensive; this might be due to the presence of different pharmacopores which might act at different locations with different mode of action. Further insights of the same can be obtained by doing investigation at receptor level. The potency of compounds 8a-8h were promising enough to continue further experiments.
authors.affiliation: Dept. of Pharm. Chem. (PG wing), A.I.S.S.M.S. College of Pharmacy, Near RTO, Kennedy Road, Pune 411001, Maharashtra, India. drugdesign1@gmail.com
authors.forename: Shashikant V
authors.initials: SV
authors.lastname: Bhandari
authors.forename: Kailash G
authors.initials: KG
authors.lastname: Bothara
authors.forename: Ajit A
authors.initials: AA
authors.lastname: Patil
authors.forename: Trupti S
authors.initials: TS
authors.lastname: Chitre
authors.forename: Aniket P
authors.initials: AP
authors.lastname: Sarkate
authors.forename: Suraj T
authors.initials: ST
authors.lastname: Gore
authors.forename: Sudarshan C
authors.initials: SC
authors.lastname: Dangre
authors.forename: Chetan V
authors.initials: CV
authors.lastname: Khachane
mesh_terms: D018674:Adrenergic Antagonists / Q000138:chemical synthesis; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D001011:Aorta; D001794:Blood Pressure / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006339:Heart Rate / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D018674:Adrenergic Antagonists; D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents