Design, synthesis, computational and biological evaluation of some new hydrazino derivatives of DHA and pyranopyrazoles

Two series of compounds namely, 4-aryl/heteroaryl hydrazino-3-acetyl-6-methyl-2H-pyran-2-ones (4a–4j) and pyrano[4,3-c]pyrazoles (6a–6e and 6g) were synthesized starting from 3-acetyl-4-chloro-6-methyl-2H-pyran-2-one (2). Estimation of pharmacotherapeutic potential, possible molecular mechanism of action, toxic/side effects and interaction with drug-metabolizing enzymes were made for the synthesized compounds on the basis of prediction of activity spectra for substances (PASS) prediction results and their analysis by PharmaExpert software. COX inhibition predicted by PASS was confirmed by experimental evaluation and validated via docking studies. Out of all the compounds, compounds 4h, 4j, 6e, 6g exhibited good anti-inflammatory activity, whereas compounds 4b, 4c, 4h, 4i, 4j, 6b, 6e, 6g showed excellent analgesic activity compared with standard drug Diclofenac sodium.

Graphical abstractTwo series of compounds namely, 4-aryl/heteroaryl hydrazino-3-acetyl-6-methyl-2H-pyran-2-ones (4a–4j) and pyrano[4,3-c]pyrazoles (6a–6e and 6g) were synthesized and evaluated for analgesic and anti-inflammatory activities. Most of the compounds displayed promising activities.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis of new hydrazino derivatives of DHA and pyrano[4,3-c]pyrazoles. ► Isolation of intermediates. ► COX inhibition predicted by PASS, confirmed by experimental evaluation. ► Docking studies. ► Compounds possessed excellent analgesic and anti-inflammatory activity.