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.
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收藏
页码：9 / 24
页数：16
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