Synthesis and Pain Inhibition Activity of the Analogs of 1-Allyl-3-Benzoylthiourea for New Analgesic Lead Compound Discovery

Alvan F. Shalas; Siswandono; Marcellino Rudyanto

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Synthesis and Pain Inhibition Activity of the Analogs of 1-Allyl-3-Benzoylthiourea for New Analgesic Lead Compound Discovery

机译：1-烯丙基-3-苯甲酰基硫脲类似物的合成及其对新型镇痛先导化合物发现的镇痛活性

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Objective: The study aimed to synthesize four analogs of 1-allyl-3-benzoylthiourea (R= H; 2-Cl; 3-Cl; and 4-Cl), and evaluate their pain inhibition activities. Method: The chemical structure was drawn assisted by Chem- Draw Ultra 8.0 and Chem3D Ultra 8.0 software. Molegro Virtual Docker 5.0 software was utilized for the docking process, to determine the interaction energy values between compounds of interest and the COX-2 receptor (PDB: 1PXX). The synthesis step was done by nucleophilic substitution (benzoylation) on allylthiourea compound via modified Schotten-Baumann reaction. Chemical structure analysis was evaluated by means of Infra-Red, Nuclear Magnetic Resonance, and Mass Spectroscopy methods. The pain inhibition assay was done using acetic acid induced writhing test, using mice ( Mus musculus) as animal model. Results: Preliminary in silico screening showed that all four candidate compounds possessed good interaction on COX-2 receptor. The synthesis process produced rendemen of the compounds vary between 15.2 %-47%. Chemical structure evaluation confirmed the structural match of the products as expected. Acetic acid induced writhing test in mice ( Mus musculus) showed that three compounds possessed a better pain inhibition activity compared to positive control diclofenac sodium. Conclusion: 1-allyl-3-benzoylthiourea analogs showed good pain inhibition activity. The compounds can serve as leads for analgesic activity through the inhibition of COX-2.

机译：目的：本研究旨在合成1-烯丙基-3-苯甲酰硫脲的四个类似物（R = H; 2-Cl; 3-Cl;和4-Cl），并评估其止痛活性。方法：在Chem-Draw Ultra 8.0和Chem3D Ultra 8.0软件的辅助下绘制化学结构。使用Molegro Virtual Docker 5.0软件进行对接过程，以确定目标化合物与COX-2受体（PDB：1PXX）之间的相互作用能值。合成步骤是通过修饰的Schotten-Baumann反应在烯丙基硫脲化合物上进行亲核取代（苯甲酰化）完成的。化学结构分析通过红外，核磁共振和质谱方法进行评估。使用乙酸（Mus musculus）作为动物模型，使用乙酸诱导的扭体试验进行疼痛抑制测定。结果：初步的计算机筛选显示，所有四种候选化合物均对COX-2受体具有良好的相互作用。合成过程中所产生的化合物含量为15.2％-47％。化学结构评估证实了产品的结构符合预期。乙酸诱导的小鼠（小家鼠）扭体试验显示，与阳性对照双氯芬酸钠相比，三种化合物具有更好的止痛活性。结论：1-烯丙基-3-苯甲酰基硫脲类似物具有良好的止痛活性。该化合物可通过抑制COX-2起到止痛作用。

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《Journal of Young Pharmacists》 |2018年第1期|共4页
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Alvan F. Shalas; Siswandono; Marcellino Rudyanto;
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Synthesis and Pain Inhibition Activity of the Analogs of 1-Allyl-3-Benzoylthiourea for New Analgesic Lead Compound Discovery

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