Zawawi Nik Khairunissa Nik Abdullah, Rajput Sajid Ali, Taha Muhammad, Ahmat Norizan, Ismail Nor Hadiani, Abdullah Noraishah, Khan Khalid Mohammed, Choudhary M Iqbal
Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D.E., Malaysia; Faculty of Applied Science, UiTM Shah Alam, 40450 Shah Alam, Selangor D.E., Malaysia.
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Centre for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Bioorg Med Chem Lett. 2015 Oct 15;25(20):4672-6. doi: 10.1016/j.bmcl.2015.08.022. Epub 2015 Aug 22.
Apoptotic cell death is the cause of the loss of insulin-producing β-cells in all forms of diabetes mellitus. The identification of small molecules capable of protecting cytokine-induced apoptosis could form the basis of useful therapeutic interventions. Here in, we present the discovery and synthesis of new benzimidazole derivatives, capable of rescuing pancreatic β-cells from cytokine-induced apoptosis. Three hydrazone derivatives of benzimidazole significantly increased the cellular ATP levels, reduced caspase-3 activity, reduced nitrite production and increased glucose-stimulated insulin secretion in the presence of proinflammatory cytokines. These findings suggest that these compounds may protect β-cells from the harmful effects of cytokines and may serve as candidates for therapeutic intervention for diabetes.
凋亡性细胞死亡是所有类型糖尿病中产生胰岛素的β细胞丧失的原因。鉴定能够保护细胞因子诱导的细胞凋亡的小分子可能构成有用治疗干预措施的基础。在此，我们展示了新型苯并咪唑衍生物的发现与合成，这些衍生物能够挽救胰腺β细胞免受细胞因子诱导的凋亡。在存在促炎细胞因子的情况下，三种苯并咪唑腙衍生物显著提高了细胞ATP水平，降低了caspase-3活性，减少了亚硝酸盐生成，并增加了葡萄糖刺激的胰岛素分泌。这些发现表明，这些化合物可能保护β细胞免受细胞因子的有害影响，并可能作为糖尿病治疗干预的候选药物。
