Abstract:
Naphthalene-based chalcone derivative was successfully synthesized through the condensation of 2,4-dichlorobenzaldehyde with 2-acetylnaphthalene. This chalcone, denoted as compound 1, demonstrated a versatile reactivity upon treatment with both nitrogen and carbon nucleophiles, and yielded diverse heterocyclic scaffolds such as pyrazoline, thiazole, pyrimidine, pyran, and pyridine derivatives. The pyrazoline aldehyde derivative 7 was further derivatized to produce the hydrazide-hydrazone 13, namely, (1H-pyrazol-1-yl)methylene)acetohydrazide, which was exploited to synthesize derivatives of 2-oxo-2H-chromene-3-carbohydrazide 14, 2-(4-oxo-4,5-dihydrothiazol-2-yl)acetohydrazide 15, and 3-(4-nitrophenyl)acrylohydrazide 16. All the newly synthesized compounds were characterized by melting point, elemental analysis, as well as FT-IR, 1 H-NMR and mass spectroscopy. Furthermore, these heterocyclic derivatives were screened for their antioxidant capacities using the DPPH radical assay. The results showed that compounds 5 and 10 are the most potent antioxidants with IC50 values 178, 177(μM), respectively. comparable to that of ascorbic acid which has IC50 value 148. Meanwhile, compounds 2, 12, 13, 14, 15, and 16 exhibited moderate antioxidant activities with IC50 values ranged from 266 to 291(μM). Thus, these heterocycles could emerge as promising antioxidant drugs for the treatment of oxidative stress-related diseases. Finally, molecular docking was conducted to study the binding affinity for the most potent antioxidant compounds 5, 10, and ascorbic acid inside the active pocket of Human Peroxiredoxin 5 (1HD2). DFT calculations and global descriptors were calculated for the most potent compounds to correlate the relation between chemical structure and reactivity.
摘要:
通过2,4-二氯苯甲醛与2-乙酰萘的缩合反应,成功合成了一种新的萘基查耳酮衍生物。这个chalcone,表示为化合物1,在用氮和碳亲核试剂处理时表现出通用的反应性,产生了多种杂环支架,如吡唑啉,噻唑,嘧啶,吡喃,和吡啶衍生物。吡唑啉醛衍生物7进一步衍生化以产生酰肼-腙13,即,(1H-吡唑-1-基)亚甲基)乙酰酰肼,用于合成2-氧代-2H-色烯-3-碳酰肼14,2-(4-氧代-4,5-二氢噻唑-2-基)乙酰酰肼15和3-(4-硝基苯基)丙烯酰肼的衍生物16。对所有新合成的化合物进行了光谱数据表征。此外,使用DPPH自由基测定法筛选这些杂环衍生物的抗氧化能力。结果表明,化合物5和10是最有效的抗氧化剂,其IC50与抗坏血酸相当。同时,化合物2、12、13、14、15和16表现出中等的抗氧化活性。因此,这些杂环可能成为治疗氧化应激相关疾病的有前途的抗氧化药物.最后,进行分子对接以研究人过氧化物酶5的活性口袋内最有效的抗氧化剂化合物5、10和抗坏血酸的结合亲和力。计算了最有效的化合物的DFT计算和全局描述符,以关联化学结构和反应性之间的关系。