背景:癌症是当今世界上最危险和最普遍的疾病之一,在过去的几十年里,它已经上升到全球主要的死亡原因。由于许多类型的癌症对常规放疗和化疗的固有抵抗力,开发创新的抗癌药物至关重要。最近,基于纳米技术的策略已被用于提高新旧抗癌药物的有效性。
目的:本研究旨在设计和合成一系列苯基异恶唑-甲酰胺衍生物,评估它们的抗癌特性,并通过使用纳米乳化剂策略提高有效化合物进入癌细胞的渗透性。
方法:使用苯胺衍生物与异恶唑-羧酸的偶联反应合成了一系列异恶唑-甲酰胺衍生物。IR,HRMS,1H-NMR,和13C-NMR光谱技术,表征了所有合成的化合物。通过使用针对7种癌细胞系的MTS测定法进行体外细胞毒性评估,包括肝细胞癌(Hep3B和HepG2),宫颈腺癌(HeLa),乳腺癌(MCF-7),黑色素瘤(B16F1),结直肠腺癌(Caco-2),和结肠腺癌(Colo205),除了正常细胞系(Hek293T)之外,还有人肝星状(LX-2)。为最有效的化合物开发了纳米乳液,使用自乳化技术。
结果:发现所有合成的化合物对B16F1、Colo205和HepG2癌细胞系具有有效至中等的活性。结果表明,2a化合物对B16F1,Colo205,HepG2和HeLa癌细胞系具有广谱活性,IC50范围为7.55-40.85µM。此外,化合物2e是对B16F1最具活性的化合物,IC50为0.079µM,与Dox相比(IC50=0.056µM)。Nanoulgel用于增加2e分子对这种癌细胞系的效力,IC50降至0.039µM。针对LX-2细胞系研究了抗纤维化活性,发现我们合成的分子在1μM时表现出比5-FU更好的抗纤维化活性,细胞活力值分别为67%和95%,分别。
结论:该研究表明2e纳米形式化化合物是一种潜在且有前景的抗黑素瘤剂。
BACKGROUND: Cancer is one of the most dangerous and widespread diseases in the world today and it has risen to the position of the leading cause of death around the globe in the last few decades. Due to the inherent resistance of many types of cancer to conventional radiotherapy and chemotherapy, it is vital to develop innovative anticancer medications. Recently, a strategy based on nanotechnology has been used to improve the effectiveness of both old and new cancer drugs.
OBJECTIVE: The present study aimed to design and synthesize a series of phenyl-isoxazole-Carboxamide derivatives, evaluate their anticancer properties, and improve the permeability of potent compounds into cancer cells by using a nano-emulgel strategy.
METHODS: The coupling reaction of aniline derivatives and isoxazole-Carboxylic acid was used to synthesize a series of isoxazole-Carboxamide derivatives. IR, HRMS, 1H-NMR, and 13C-NMR spectroscopy techniques, characterized all the synthesized compounds. The in-vitro cytotoxic evaluation was performed by using the MTS assay against seven cancer cell lines, including hepatocellular carcinoma (Hep3B and HepG2), cervical adenocarcinoma (HeLa), breast carcinoma (MCF-7), melanoma (
B16F1), colorectal adenocarcinoma (Caco-2), and colon adenocarcinoma (Colo205), as well as human hepatic stellate (LX-2) in addition to the normal cell line (Hek293T). A nano-emulgel was developed for the most potent compound, using a self-emulsifying technique.
RESULTS: All synthesized compounds were found to have potent to moderate activities against
B16F1, Colo205, and HepG2 cancer cell lines. The results revealed that the 2a compound has broad spectrum activity against
B16F1, Colo205, HepG2, and HeLa cancer cell lines with an IC50 range of 7.55-40.85 µM. Moreover, compound 2e was the most active compound against
B16F1 with an IC50 of 0.079 µM compared with Dox (IC50 = 0.056 µM). Nanoemulgel was used to increase the potency of the 2e molecule against this cancer cell line, and the IC50 was reduced to 0.039 µM. The antifibrotic activities were investigated against the LX-2 cell line, and it was found that our synthesized molecules showed better antifibrotic activities at 1 µM than 5-FU, and the cell viability values were 67 and 95%, respectively.
CONCLUSIONS: This study suggests that a 2e nano-formalized compound is a potential and promising anti-melanoma agent.