Pancreatic lipase (PL) plays a major role in the hydrolysis of dietary triglycerides to monoglycerides and free fatty acids in the small intestine before absorption of fats. The excessive consumption of dietary fat (triglyceride) and not to utilize it for energy production can cause an increase in obesity. Obesity is one of the serious health problem in the world and leads to many diseases such as some types of cancer, heart disease, gallstones, sleep apnea, fatty liver disease, type-2 diabetes, hypertension, coronary artery disease. Therefore, lipase is the target enzyme to prevent these diseases and the inhibitors of lipase are very important molecules as drug candidate molecules. In this study, fifteen new heterocyclic compounds have been synthesized starting from 2-[3-(4-chlorobenzyl)-5-(4-chlorophenyl)-1H-1,2,4-triazol-4-yl]-acetohydrazide and their anti-lipase activities have been examined. According to in vitro inhibition studies, molecule 2e is found to be the most potent inhibitor with the lowest IC₅₀ value. Docking studies' results have substantially supported this result and it is seen that compound 2e is one of the four molecules with the highest binding affinity. This molecule binds to the enzyme in its binding pocket by means of weak interactions with mainly Ile79, Asp80, Val260, Arg257 and His264.

中文翻译：

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取代的1,2,4-三唑衍生物的脂肪酶抑制活性合成与评价

胰腺脂肪酶（PL）在饮食中的甘油三酸酯在脂肪吸收前水解为甘油三酸酯和游离脂肪酸中起主要作用。饮食脂肪（甘油三酸酯）的过多消耗以及不将其用于产生能量会导致肥胖症增加。肥胖是世界上严重的健康问题之一，并导致许多疾病，例如某些类型的癌症，心脏病，胆结石，睡眠呼吸暂停，脂肪肝疾病，2型糖尿病，高血压，冠状动脉疾病。因此，脂肪酶是预防这些疾病的目标酶，并且脂肪酶的抑制剂是作为候选药物分子非常重要的分子。在这项研究中，从2- [3-（4-氯苄基）-5-（4-氯苯基）-1 H开始合成了15种新的杂环化合物已经研究了-1,2,4-三唑4-基]-乙酰肼及其抗脂肪酶活性。根据体外抑制研究，发现分子2e是最有效的抑制剂，具有最低的IC ₅₀值。对接研究的结果基本上支持了这一结果，并且可以看出化合物2e是具有最高结合亲和力的四个分子之一。该分子通过主要与Ile79，Asp80，Val260，Arg257和His264的弱相互作用与结合袋中的酶结合。