Hawash Mohammed, Jaradat Nidal, Eid Ahmad M, Abubaker Ahmad, Mufleh Ola, Al-Hroub Qusay, Sobuh Shorooq
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine.
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine.
BMC Chem. 2022 Jun 24;16(1):47. doi: 10.1186/s13065-022-00839-5.
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.
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.
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.
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 IC range of 7.55-40.85 µM. Moreover, compound 2e was the most active compound against B16F1 with an IC of 0.079 µM compared with Dox (IC = 0.056 µM). Nanoemulgel was used to increase the potency of the 2e molecule against this cancer cell line, and the IC 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.
This study suggests that a 2e nano-formalized compound is a potential and promising anti-melanoma agent.
癌症是当今世界上最危险且分布广泛的疾病之一，在过去几十年中已上升至全球主要死因的位置。由于多种类型的癌症对传统放疗和化疗具有内在抗性，开发创新的抗癌药物至关重要。最近，一种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。
本研究旨在设计并合成一系列苯基异恶唑 - 甲酰胺衍生物，评估其抗癌特性，并通过纳米乳凝胶策略提高强效化合物对癌细胞的渗透性。
采用苯胺衍生物与异恶唑羧酸的偶联反应合成一系列异恶唑 - 甲酰胺衍生物。利用红外光谱（IR）、高分辨质谱（HRMS）、氢核磁共振（1H - NMR）和碳核磁共振（13C - NMR）光谱技术对所有合成化合物进行表征。通过MTS法对七种癌细胞系进行体外细胞毒性评估，包括肝癌细胞系（Hep3B和HepG2）、宫颈腺癌细胞系（HeLa）、乳腺癌细胞系（MCF - 7）、黑色素瘤细胞系（B16F1）、结肠腺癌细胞系（Caco - 2）和结肠腺癌细胞系（Colo205），以及除正常细胞系（Hek293T）外的人肝星状细胞系（LX - 2）。采用自乳化技术为最有效的化合物制备纳米乳凝胶。
所有合成化合物对B16F1、Colo205和HepG2癌细胞系均表现出强效至中等活性。结果显示，化合物2a对B16F1、Colo205、HepG2和HeLa癌细胞系具有广谱活性，IC范围为7.55 - 40.85 μM。此外，与阿霉素（IC = 0.056 μM）相比，化合物2e是对B16F1最具活性的化合物，IC为0.079 μM。纳米乳凝胶用于提高2e分子对该癌细胞系的效力，IC降至0.039 μM。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1 μM时比5 - 氟尿嘧啶表现出更好的抗纤维化活性，细胞活力值分别为67%和95%。
本研究表明，2e纳米化化合物是一种有潜力且有前景的抗黑色素瘤药物。
