One-pot synthesis, biological evaluation, and docking study of new chromeno-annulated thiopyrano[2,3-c]pyrazoles

• Published in: Molecular diversity 2016-08, Vol.20 (3), p.639-657
• Main Authors: Parmar, Bhagyashri D., Sutariya, Tushar R., Brahmbhatt, Gaurangkumar C., Parmar, Narsidas J., Kant, Rajni, Gupta, Vivek K., Murumkar, Prashant R., Sharma, Mayank Kumar, Yadav, Mange Ram
• Format: Article
• Language: English
• Subjects: Angiotensin I - metabolism; Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Benzopyrans - chemical synthesis; Benzopyrans - chemistry; Benzopyrans - pharmacology; Biochemistry; Biomedical and Life Sciences; Catalytic Domain - drug effects; Chemical compounds; Chemical reactions; Chemical synthesis; Cycloaddition Reaction; Life Sciences; Molecular Docking Simulation; Molecular Structure; Organic Chemistry; Original Article; Pharmacy; Polymer Sciences; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Structure-Activity Relationship
• ISSN: 1381-1991; 1573-501X
• DOI: 10.1007/s11030-016-9665-z

A one-pot synthesis of new chromeno-annulated thiopyrano[2,3- c ]pyrazoles has been achieved through a domino-Knoevenagel– hetero -Diels–Alder reaction after combining various pyrazol-5-thiones with O -alkenyloxy/alkynyloxy-salicylaldehydes/naphthaldehydes in a Brønsted acidic ionic liquid, [Hmim]HSO 4 , methylimidazolium hydrogen sulphate, under microwave irradiation. The method is simple and in many cases the isolated products did not require further purification. The central pyranothiopyranyl cis -fusion was confirmed by 2D NMR NOESY and single-crystal X-ray analysis suggesting that the endo-E-Syn transition state would be the most favored pathway of the reaction. Many heterocycles of this new series were found active against six bacterial and two fungal strains. In addition, all the compounds possess good anti-oxidant activity with the ferric reducing anti-oxidant power value > 100 mmol / 100 g . All new structures were docked into active site of angiotensin I converting enzyme (ACE), assuming that the compounds possessed the anti-hypertensive activity potential on the basis of prediction of activity spectra of substances prediction results. Pyranyl ring oxygen in compound 9a forms two hydrogen bonds with HIS353 and HIS513 residues in the active site of the ACE having good G score ( - 4.06 ) of this compound, comparable to that of the reference drug captopril ( - 4.93 ). Graphical Abstract