Anantacharya Rajpurohit, Satyanarayan Nayak D, Sukhlal Kalal Bhuvanesh, Pai Vinitha Ramanath
Department of Pharmaceutical Chemistry, Kuvempu University, Post Graduate Centre, Kadur, 577548, Chikkamagalur Dist, Karnataka, India.
Department of Biochemistry, Yenepoya Medical College, Yenepoya University, Mangaluru, 575018, Karnataka, India.
Open Med Chem J. 2018 May 31;12:60-72. doi: 10.2174/1874104501812010060. eCollection 2018.
Furan, quinoline and triazoles are known for their wide spectrum biologically active molecules. A series of novel furan C-2 quinoline and 1, 2, 4-triazole (FQT) coupled hybrids were designed and synthesized to evaluate for their DNA cleavage and cytotoxic studies.
In this work we describe the synthesis and biological evaluation of furan C-2 quinoline coupled triazoles exposed for cytotoxic and DNA cleavage study.
The electrophoretic DNA cleavage studies on λ-DNA (Eco-RI/Hinda-III double digest) using agarose gelelectrophoresis and the cytotoxic activity were carried out by MTT assay method.
The results revealed that, the molecules 7(a-o) did cleave the DNA completely with no trace of fragments at 100 µg concentration, on the other hand, cytotoxic assay was achieved by two different human cancer cell lines (melanoma cell line-A375 and breast cancer cell line MDA-MB 231). Among the synthesized compounds 7a, 7b, 7c and 7k exhibited potent cytotoxic activity with IC values ranging from 2.9, 4.0, 7.8 and 5.1 µg/ml against A375 and 6.2, 9.5, 11.3 and 7.3 µg/ml against, MDA-MB 231, respectively.
In synthesized compounds 7(a-o) exhibited complete DNA cleavage at 100 µg/ml and the compounds 7a, 7b, 7c and 7k showed very less cytotoxic in nature. The structure activity relationship revealed that, the presence of halogen group/atoms at para position of phenyl ring remarkably enhanced the DNA cleavage and cytotoxic activities among the synthesized compounds.
呋喃、喹啉和三唑以其广泛的生物活性分子谱而闻名。设计并合成了一系列新型的呋喃C-2喹啉与1,2,4-三唑（FQT）偶联的杂化物，以评估其DNA裂解和细胞毒性研究。
在本研究中，我们描述了用于细胞毒性和DNA裂解研究的呋喃C-2喹啉偶联三唑的合成及生物学评价。
使用琼脂糖凝胶电泳对λ-DNA（Eco-RI/Hinda-III双酶切）进行电泳DNA裂解研究，并通过MTT法进行细胞毒性活性测定。
结果显示，在100μg浓度下，分子7（a-o）能完全裂解DNA且无片段痕迹，另一方面，通过两种不同的人类癌细胞系（黑色素瘤细胞系-A375和乳腺癌细胞系MDA-MB 231）进行了细胞毒性测定。在合成的化合物中，7a、7b、7c和7k表现出较强的细胞毒性活性，对A375的IC值分别为2.9、4.0、7.8和5.1μg/ml，对MDA-MB 231的IC值分别为6.2、9.5、11.3和7.3μg/ml。
在合成的化合物7（a-o）中，在100μg/ml时表现出完全的DNA裂解，而化合物7a、7b、7c和7k在本质上显示出非常低的细胞毒性。构效关系表明，苯环对位存在卤素基团/原子显著增强了合成化合物中的DNA裂解和细胞毒性活性。
