Sehlangia Suman, Nayak Namyashree, Garg Neha, Pradeep Chullikkattil P
School of Basic Sciences, Indian Institute of Technology Mandi, Kamand 175005, Himachal Pradesh, India.
Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India.
ACS Omega. 2022 Jul 8;7(28):24838-24850. doi: 10.1021/acsomega.2c03047. eCollection 2022 Jul 19.
Styryl quinolines are biologically active compounds with properties largely depending on the substituents on the styryl and quinoline rings. The supramolecular aspects of this class of compounds are rarely explored. In this study, two new series of styryl quinoline derivatives, bearing -OH and -NO groups at the eighthposition of the quinoline ring and -SCH, -OCH, and -Br groups on the styryl ring, have been developed, and their structural, supramolecular, and cytotoxic properties have been analyzed. Crystallographic analyses revealed the exciting substituent-dependent structural and supramolecular features of these compounds. In general, the 8 -OH substituted derivatives ( series) exhibited a non-planar molecular geometry having larger dihedral angles (5.75-59.3°) between the planes of the aromatic rings. At the same time, the 8 -NO substituted derivatives ( series) exhibited a more or less planar molecular geometry, as revealed by the smaller dihedral angles (1.32-3.45°) between the aromatic rings. Multiple O-H···O, C-H···O, O-H···N, and π-π stacking interactions among the molecules lead to fascinating supramolecular architectures such as hydrogen-bonded triple helices, zig-zag 1D chains, π-π stacked infinite chains, and so forth in their crystal lattice. Hirshfeld surface analyses confirmed the existence of strong π-π stacking and other weak bonding interactions in these compounds. The preliminary cytotoxic properties of and series compounds were evaluated against the human cervical cancer cell lines (HeLa cells), which further highlighted the roles of functional substituents on the aromatic rings. The series compounds with the -OH substituent on the quinoline ring exhibited better cytotoxicity than the series compounds with a -NO substituent. Similarly, the electron-withdrawing group -Br on the styryl ring enhanced the cytotoxicity in both series. The IC values were 2.52-4.69 and 2.897-10.37 μM, respectively, for the and series compounds. Compound having -OH and -Br groups on the quinoline and styryl ring, respectively, exhibited the best IC value of 2.52 μM among all the compounds tested. These findings confirm the relevance of the hydroxyl group in the eighth position of quinoline. In short, the present study attempts to provide a systematic analysis of the effects of aromatic ring substituents on the structural, supramolecular, and cytotoxic properties of styryl quinolines for the first time.
苯乙烯基喹啉是一类生物活性化合物，其性质很大程度上取决于苯乙烯基和喹啉环上的取代基。这类化合物的超分子方面很少被研究。在本研究中，已开发出两个新系列的苯乙烯基喹啉衍生物，它们在喹啉环的第八位带有 -OH 和 -NO 基团，在苯乙烯基环上带有 -SCH₃、-OCH₃ 和 -Br 基团，并对其结构、超分子和细胞毒性性质进行了分析。晶体学分析揭示了这些化合物令人兴奋的、依赖于取代基的结构和超分子特征。一般来说，8 -OH 取代的衍生物（系列）呈现出非平面分子几何结构，芳环平面之间具有较大的二面角（5.75 - 59.3°）。同时，8 -NO 取代的衍生物（系列）呈现出或多或少的平面分子几何结构，芳环之间的二面角较小（1.32 - 3.45°）。分子间多种 O-H···O、C-H···O、O-H···N 和 π-π 堆积相互作用导致其晶格中形成了迷人的超分子结构，如氢键连接的三螺旋、之字形一维链、π-π 堆积的无限链等。Hirshfeld 表面分析证实了这些化合物中存在强 π-π 堆积和其他弱键相互作用。对 系列和 系列化合物针对人宫颈癌细胞系（HeLa 细胞）的初步细胞毒性性质进行了评估，这进一步突出了芳环上功能取代基的作用。喹啉环上带有 -OH 取代基的 系列化合物比带有 -NO 取代基的 系列化合物表现出更好的细胞毒性。同样，苯乙烯基环上的吸电子基团 -Br 在两个系列中都增强了细胞毒性。 系列和 系列化合物的 IC₅₀ 值分别为 2.52 - 4.6 和 2.897 - 10.37 μM。在所有测试化合物中，喹啉环和苯乙烯基环上分别带有 -OH 和 -Br 基团的化合物 表现出最佳的 IC₅₀ 值 2.52 μM。这些发现证实了喹啉第八位羟基的重要性。简而言之，本研究首次尝试对芳环取代基对苯乙烯基喹啉的结构、超分子和细胞毒性性质的影响进行系统分析。
