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

被引：9

作者：

Sharma, Shweta ^{[1
,5
]}

Ansari, Mohd. Hafizur Rehman ^{[2
]}

Sharma, Kalicharan

Singh, Rajesh K. ^{[3
]}

Ali, Shakir ^{[4
,5
]}

Alam, Mohd. Mumtaz ^{[1
]}

Zaman, Mohd. Shaqiquzamman ^{[1
]}

Alam, Prawez ^{[6
]}

Akhter, Mymoona ^{[1
,5
]}

机构：

[1] Jamia Hamdard, Sch Pharmaceut Educ & Res, Dept Pharmaceut Chem, Drug Design & Med Chem Lab, New Delhi 110062, India

[2] Jamia Hamdard, Fac Pharm, Dept Pharmacognosy & Phytochemistry, Bioact Nat Prod Lab, New Delhi 110062, India

[3] Shivalik Coll Pharm, Dept Pharmaceut Chem, Nangal 140126, Punjab, India

[4] Jamia Hamdard, Sch Chem & Biol Sci, Dept Biochem, New Delhi 110062, India

[5] Jamia Hamdard, Bioinformat Infrastructure Facil, New Delhi 110062, India

[6] Prince Sattam Bin Abdulaziz Univ, Dept Pharmacognosy, Coll Pharm, Al kharj 11942, Saudi Arabia

来源：

FUTURE MEDICINAL CHEMISTRY | 2023年 / 15卷 / 01期

关键词：

antidiabetic; docking; DPP-IV; in silico; oral glucose tolerance test; pyrazoline; DIPEPTIDYL-PEPTIDASE-IV; SCREENING LIBRARIES; INHIBITORS; DISCOVERY; POTENT; ANALOGS; DESIGN;

D O I：

10.4155/fmc-2022-0141

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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-1H-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 IC50 values of 0.10 mu M, 0.12 mu M and 0.35 mu M, 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.

引用

页码：9 / 24

页数：16

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