Zelelew Demis, Endale Milkyas, Melaku Yadessa, Geremew Teshome, Eswaramoorthy Rajalakshmanan, Tufa Lemma Teshome, Choi Youngeun, Lee Jaebeom
Department of Applied Chemistry, School of Applied Natural Science, Adama Science and Technology University, Adama, Ethiopia.
Department of Applied Biology, School of Applied Natural Science, Adama Science and Technology University, Adama, Ethiopia.
Adv Appl Bioinform Chem. 2023 Jul 28;16:61-91. doi: 10.2147/AABC.S403413. eCollection 2023.
Heterocyclic analogs of curcumin have a wide range of therapeutic potential and the ability to control the activity of a variety of metabolic enzymes.
H-NMR and C-NMR spectroscopic techniques were used to determine the structures of synthesized compounds. The agar disc diffusion method and α-amylase inhibition assay were used to examine the antibacterial and anti-diabetic potential of the compounds against α-amylase enzyme inhibitory activity, respectively. DPPH-free radical scavenging and lipid peroxidation inhibition assays were used to assess the in vitro antioxidant potential.
In this work, nine heterocyclic analogs derived from curcumin precursors under ultrasonic irradiation were synthesized in excellent yields (81.4-93.7%) with improved reaction time. Results of antibacterial activities revealed that compounds 8, and 11 displayed mean inhibition zone of 13.00±0.57, and 19.66±00 mm, respectively, compared to amoxicillin (12.87±1.41 mm) at 500 μg/mL against , while compounds 8, 11 and 16 displayed mean inhibition zone of 17.67±0.57, 14.33±0.57 and 23.33±00 mm, respectively, compared to amoxicillin (13.75±1.83 mm) at 500 μg/mL against . Compound 11 displayed a mean inhibition zone of 11.33±0.57 mm compared to amoxicillin (10.75±1.83 mm) at 500 μg/mL against . Compound 11 displayed higher binding affinities of -7.5 and -8.3 Kcal/mol with penicillin-binding proteins (PBPs) and -lactamases producing bacterial strains, compared to amoxicillin (-7.2 and -7.9 Kcal/mol, respectively), these results are in good agreement with the in vitro antibacterial activities. In vitro antidiabetic potential on -amylase enzyme revealed that compounds 11 (IC=7.59 µg/mL) and 16 (IC=4.08 µg/mL) have higher inhibitory activities than acarbose (IC=8.0 µg/mL). Compound 8 showed promising antioxidant inhibition efficacy of DPPH (IC = 2.44 g/mL) compared to ascorbic acid (IC=1.24 g/mL), while compound 16 revealed 89.9±20.42% inhibition of peroxide generation showing its potential in reducing the development of lipid peroxides. In silico molecular docking analysis, results are in good agreement with in vitro biological activity. In silico ADMET profiles suggested the adequate oral drug-likeness potential of the compounds without adverse effects.
According to our findings, both biological activities and in silico computational studies results demonstrated that compounds 8, 11, and 16 are promising -amylase inhibitors and antibacterial agents against , , and , whereas compound 8 was found to be a promising antioxidant agent.
姜黄素的杂环类似物具有广泛的治疗潜力，并有能力控制多种代谢酶的活性。
采用氢核磁共振（H-NMR）和碳核磁共振（C-NMR）光谱技术确定合成化合物的结构。分别采用琼脂平板扩散法和α-淀粉酶抑制试验检测化合物对α-淀粉酶的抗菌和抗糖尿病潜力以及酶抑制活性。采用二苯基苦味酰基自由基（DPPH）清除试验和脂质过氧化抑制试验评估体外抗氧化潜力。
在本研究中，在超声辐射下由姜黄素前体衍生得到的9种杂环类似物以优异的产率（81.4 - 93.7%）合成，且反应时间缩短。抗菌活性结果显示，在500μg/mL浓度下，与阿莫西林（12.87±1.41mm）相比，化合物8和11对[具体细菌名称1]的平均抑菌圈分别为13.00±0.57mm和19.66±0.00mm；与阿莫西林（13.75±1.83mm）相比，化合物8、11和16对[具体细菌名称2]的平均抑菌圈分别为17.67±0.57mm、14.33±0.57mm和23.33±0.00mm。与阿莫西林（10.75±1.83mm）相比，化合物11对[具体细菌名称3]在500μg/mL浓度下的平均抑菌圈为11.33±0.57mm。与阿莫西林（分别为-7.2和-7.9Kcal/mol）相比，化合物11与青霉素结合蛋白（PBPs）和产生β-内酰胺酶的细菌菌株具有更高的结合亲和力，分别为-7.5和-8.3Kcal/mol，这些结果与体外抗菌活性良好一致。对α-淀粉酶的体外抗糖尿病潜力研究表明，化合物11（IC50 = 7.59μg/mL）和16（IC50 = 4.08μg/mL）比阿卡波糖（IC50 = 8.0μg/mL）具有更高的抑制活性。与抗坏血酸（IC50 = 1.24μg/mL）相比，化合物8对DPPH显示出有前景的抗氧化抑制效果（IC50 = 2.44μg/mL），而化合物16显示出89.9±20.42%的过氧化物生成抑制率，表明其在减少脂质过氧化物形成方面的潜力。在计算机模拟分子对接分析中，结果与体外生物活性良好一致。计算机模拟的药物代谢动力学/药物毒性（ADMET）概况表明这些化合物具有足够的口服类药物潜力且无不良反应。
根据我们的研究结果，生物活性和计算机模拟计算研究结果均表明，化合物8、11和16是有前景的针对[具体细菌名称1]、[具体细菌名称2]和[具体细菌名称3]的α-淀粉酶抑制剂和抗菌剂，而化合物8被发现是一种有前景的抗氧化剂。
