Synthesis, In Vitro, and In Silico Studies of N-(Substituted-Phenyl)-3-(4-Phenyl-1-Piperazinyl)propanamides as Potent Alkaline Phosphatase Inhibitors

• Published in: Russian Journal of Bioorganic Chemistry
• Main Author: Abbasi M.A.; Nazir M.; Aziz-ur-Rehman; Siddiqui S.Z.; Raza H.; Zafar A.; Shah S.A.A.; Shahid M.
• Format: Article
• Language: English
• Published: Pleiades journals 2021
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85117566596&doi=10.1134%2fS1068162021050186&partnerID=40&md5=84d9a5a04753fd680e94e193cd517c89

Abstract: In the present research work, a new series of N-(substituted-phenyl)-3-(4-phenyl-1-piperazinyl)propanamides were synthesized. The synthesis was initiated by the coupling of different aromatic amines with 3-bromopropanoyl chloride in aqueous basic medium, to synthesize different electrophiles with good yields. These electrophiles were further reacted with 1-phenylpiperazine to yield the desired compounds, N-(substituted-phenyl)-3-(4-phenyl-1-piperazinyl)propanamides as depicted in scheme 1. The structural confirmation of all the synthesized compounds was corroborated by IR, 1H NMR, 13C NMR, HMBC and CHN analysis data. The in vitro inhibitory potential of these propanamides was evaluated against alkaline phosphatase enzyme and it was explored that all these molecules exhibit potent inhibition relative to the standard used. The Kinetics mechanism analyzed by Lineweaver-Burk plots which exposed that N-(4-ethylphenyl)-3-(4-phenyl-1-piperazinyl)propanamide inhibited this enzyme competitively by forming an enzyme-inhibitor complex. Moreover, these compounds were studied for cytotoxic behaviour by hemolytic activity, whereby it was avowed that nearly all these propanamides disclosed low cytotoxicity. In addition, kinetic analysis were also carried out to understand the mode of inhibition for these compounds. The in silico investigation of these compounds was also in agreement with the in vitro results. So, it was envisaged that these derivatives might lead to further research gateways for obtaining better and safe as nontoxic medicinal scaffolds for dealing with the alkaline phasphatase related ailments such as bone diseases, diabetes, prostatic cancer and liver dysfunction. © 2021, Pleiades Publishing, Ltd.