Pyrazoline scaffold: hit identification to lead synthesis and biological evaluation as antidiabetic agents.

Autor:	Sharma S; Department of Pharmaceutical Chemistry, Drug Design & Medicinal Chemistry Lab, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India.; Bioinformatics Infrastructure Facility, Jamia Hamdard, New Delhi, 110062, India., Rehman Ansari MH; Department of Pharmacognosy & Phytochemistry, Bioactive Natural Product Laboratory, Faculty of Pharmacy, Jamia Hamdard, New Delhi, 110062, India., Sharma K, Singh RK; Department of Pharmaceutical Chemistry, Shivalik College of Pharmacy, Nangal, Punjab, 140126, India., Ali S; Department of Biochemistry, School of Chemical & Biological Sciences, Jamia Hamdard, New Delhi, 110062, India.; Bioinformatics Infrastructure Facility, Jamia Hamdard, New Delhi, 110062, India., Alam MM; Department of Pharmaceutical Chemistry, Drug Design & Medicinal Chemistry Lab, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India., Zaman MS; Department of Pharmaceutical Chemistry, Drug Design & Medicinal Chemistry Lab, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India., Alam P; Department of Pharmacognosy College of Pharmacy Prince Sattam Bin, Abdulaziz University, Al-kharj, 11942, Saudi Arabia., Akhter M; Department of Pharmaceutical Chemistry, Drug Design & Medicinal Chemistry Lab, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India.; Bioinformatics Infrastructure Facility, Jamia Hamdard, New Delhi, 110062, India.
Jazyk:	angličtina
Zdroj:	Future medicinal chemistry [Future Med Chem] 2023 Jan; Vol. 15 (1), pp. 9-24. Date of Electronic Publication: 2023 Jan 19.
DOI:	10.4155/fmc-2022-0141
Abstrakt:	Background: Mining of novel scaffolds as potential DPP-IV inhibitors for future development of potential candidates as antidiabetic agents to address global issues. Methodology: The identified hit KB-10 from a previously reported study was taken as a lead for designing a library of analogues and screened initially based on in silico parameters and docking score. A series of selected (2[4-(1-acetyl-5-phenyl-4,5-dihydro-1 H -pyrazol-3-yl)phenoxy]-1-phenylethanone derivatives were synthesized and evaluated through in vitro studies. Compounds KB-23 , KB-22 and KB-06 were found to be as potent, with IC 50 values of 0.10 μM, 0.12 μM and 0.35 μM, respectively. They also showed promising antihyperglycemic potential in in vivo studies (oral glucose tolerance tests) in Wistar rats. Conclusion: This work establishes pyrazoline analogues KB-23 , KB-22 and KB-06 as promising starting points for the development of potential antidiabetic agents.
Databáze:	MEDLINE
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