Department of Chemistry, Government College University, Faisalabad, Pakistan.
Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.
Pak J Pharm Sci. 2020 Mar;33(2(Supplementary)):847-854.
Pyrazoline and benzimidazoles derivatives have been widely studied due to their potential applications in the medicinal field. In this research project, we have hybridized these two heterocyclic systems in the same molecule. A new series of compounds, 2-((3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)methyl)-1H-benzo[d]imidazole (5a-i) were synthesized through a multistep reaction. In the first step, chalcones 3a-i were prepared by coupling of various acetophenones and benzaldehydes under alkaline conditions. These chalcones were cyclized with hydrazine hydrate to form a series of pyrazolines which were finally coupled with 2-chloromethyl-1H-benzimidazole to get a new series of titled hybrid molecules. The structures of these compounds were elucidated by spectral (1H NMR and 13C NMR) analysis. The anti-diabetic potential of these compounds was studied by screening them for their α-glucosidase inhibition activity. The SAR was established through molecular docking analysis. Compound 5d appeared as effective inhibitor with IC = 50.06μM as compared to reference drug (acarbose) having IC = 58.8μM.
由于其在医学领域的潜在应用，吡唑啉和苯并咪唑衍生物一直受到广泛研究。在这个研究项目中，我们将这两种杂环系统在同一个分子中进行了杂交。通过多步反应合成了一系列新的化合物 2-((3,5-二芳基-4,5-二氢-1H-吡唑-1-基)甲基)-1H-苯并[d]咪唑（5a-i）。在第一步中，通过碱性条件下各种苯乙酮和苯甲醛的偶联制备查耳酮 3a-i。这些查耳酮与水合肼环化形成一系列吡唑啉，最后与 2-氯甲基-1H-苯并咪唑偶联得到一系列标题杂化分子。通过光谱（1H NMR 和 13C NMR）分析阐明了这些化合物的结构。通过筛选它们对α-葡萄糖苷酶抑制活性来研究这些化合物的抗糖尿病潜力。通过分子对接分析建立了 SAR。与对照药物（阿卡波糖）的 IC = 58.8μM 相比，化合物 5d 作为有效的抑制剂，IC = 50.06μM。
