背景:苯并[d]噻唑代表了一类重要的杂环化合物,以其多种药理活性而闻名,包括镇痛和抗炎特性。由于其结构多功能性和治疗潜力,这种分子支架在药物化学家中引起了极大的兴趣。已广泛研究了将苯并[d]噻唑部分掺入药物分子中作为制备具有提高的功效和最小化的副作用的新型治疗剂的策略。
目的:本研究工作的目的是设计,合成并表征新的苯并[d]噻唑-2-胺衍生物作为有效的镇痛药和抗炎药。
方法:本发明的苯并[d]噻唑-2-胺衍生物的合成是通过在碘化钾和无水碳酸钾的存在下,在无水丙酮中,将-(4-氯苄基)苯并[d]噻唑-2-胺与许多取代的酚缩合来进行的。红外光谱,1HNMR光谱,13CNMR光谱和质谱方法用于表征所有13个新合成的衍生物的结构性质。估计这些新合成的衍生物的分子性质以研究药物样候选物的属性。苯并[d]噻唑-2-胺衍生物与选择性酶COX-1和COX-2分子对接。用白化病大鼠评价了合成化合物的镇痛和抗炎活性。
结果:研究结果表明,化合物G3,G4,G6,G8和G11具有比双氯芬酸钠更高的结合亲和力,当与酶COX-1进行对接时。当用酶COX-2进行对接时,化合物G1、G3、G6、G8andG10显示出比吲哚美辛更低的结合亲和力。对合成的化合物进行COX-1和COX-2酶抑制活性的体外评价。
结论:化合物G10和G11表现出显著的COX-1和COX-2酶抑制作用,IC50值为5.0和10μM,分别。采用热板法和角叉菜胶致大鼠爪水肿模型,对合成的化合物进行生物活性筛选,包括镇痛和抗炎活性。衍生物G11表现出最高的镇痛作用,化合物G10表现出最高的抗炎反应。COX的抑制可以被认为是这些化合物的作用机制。
结论:结论是合成的衍生物G10和G11具有明显的镇痛和抗炎作用;因此,所述化合物可以进行进一步的临床研究,以确定这些化合物作为治疗疼痛和炎症的未来化合物。
BACKGROUND: Benzo[d]thiazoles represent a significant class of heterocyclic com-pounds renowned for their diverse pharmacological activities, including analgesic and anti-inflammatory properties. This molecular scaffold holds substantial interest among medicinal chemists owing to its structural versatility and therapeutic potential. Incorporating the benzo[d]thiazole moiety into drug molecules has been extensively investigated as a strategy to craft novel therapeutics with heightened efficacy and minimized adverse effects.
OBJECTIVE: The aim of the present research work was to design, synthesize and characterize the new benzo[d]thiazol-2-amine derivatives as potent analgesic and anti-inflammatory agents.
METHODS: The synthesis of the presented benzo[d]thiazol-2-amine derivatives was performed by condensing-(4-chlorobenzylidene) benzo[d]thiazol-2-amine with a number of substituted phenols in the presence of potassium iodide and anhydrous potassium carbonate in dry acetone. IR spectroscopy, 1HNMR spectroscopy, 13CNMR spectroscopy and Mass spectroscopy methods were used to characterize the structural properties of all 13 newly syn-thesized derivatives. The molecular properties of these newly synthesized derivatives were estimated to study the attributes of drug-like candidates. Benzo[d]thiazol-2-amine derivatives were molecularly docked with selective enzymes COX-1 and COX-2. Analgesic and anti-inflammatory activities of synthesized compounds were evaluated by us-ing albino rats.
RESULTS: Findings of the research suggested that compounds G3, G4, G6, G8 and G11 possess higher binding affinity than diclofenac sodium, when docking was performed with enzyme COX-1. Compounds G1, G3, G6, G8andG10 showed lower binding affinity than Indometha-cin when docking was performed with enzyme COX-2.In vitro evaluation of the COX-1 and COX-2 enzyme inhibitory activities was performed for synthesized compounds.
CONCLUSIONS: Compounds G10 and G11 exhibited significant COX-1 and COX-2 enzyme in-hibitory action with an IC50 value of 5.0 and 10 μM, respectively. Using the hot plate method and the carrageenan-induced rat paw edema model, the synthesized compounds were screened for their biological activities, including analgesic and anti-inflammatory activities. Highest analgesic action was exhibited by derivative G11 and the compound G10 showed the highest anti-inflammatory response. Inhibition of COX may be considered as a mechanism of action of these compounds.
CONCLUSIONS: It was concluded that synthesized derivatives G10 and G11 exhibited significant analgesic and anti-inflammatory effect; therefore, the said compounds may be subjected to further clinical investigation for establishing these as future compounds for the treatment of pain and inflammation.