Substituent-Controlled Structural, Supramolecular, and Cytotoxic Properties of a Series of 2-Styryl-8-nitro and 2-Styryl-8-hydroxy Quinolines

Abstract

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 2 groups at the eighthposition of the quinoline ring and −SCH 3 , −OCH 3 , 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 ( SA 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 2 substituted derivatives ( SB 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 SA and SB 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 SA series compounds with the −OH substituent on the quinoline ring exhibited better cytotoxicity than the SB series compounds with a −NO 2 substituent. Similarly, the electron-withdrawing group −Br on the styryl ring enhanced the cytotoxicity in both series. The IC 50 values were 2.52–4.69 and 2.897–10.37 μM, respectively, for the SA and SB series compounds. Compound S3A having −OH and −Br groups on the quinoline and styryl ring, respectively, exhibited the best IC 50 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.

New 8-hydroxy quinoline-polycyclic aromatic hydrocarbon (PAH) conjugates and their sulfonated derivatives: effects of sulfonation and PAH size on their structural, supramolecular and cytotoxic properties

“…† All these compounds, PD1-PD3, exhibited 1 H NMR peaks in the range 6.72-8.28 ppm with J values of 15.8-16.5 ppm, confirming the presence of trans vinylene groups. 28,32 Single crystals of PH and PD series compounds suitable for crystallographic analyses were grown from a mixture of methanol and dichloromethane by the slow evaporation method. The molecular structures of these compounds were confirmed by single-crystal X-ray diffraction analyses.…”

“…The C10-C11 bond distances are 1.316(4) Å and 1.332(3) Å, respectively, for PH1 and PH3, characteristic of a typical styryl double bond, as reported earlier. 28,32,47 The crystal packing of PH1 is dominated by intermolecular C-H⋯O and C-H⋯π interactions; see Tables S2 and S3 in ESI † for details. In the unit cell, a pair of adjacent molecules are oriented in almost perpendicular directions (dihedral angle between the mean planes of the molecules = 82.22°), as shown in Fig.…”

“…Similar supramolecular assembles of 3D networks generated from C-H⋯O and C-H⋯π interactions have been reported in the literature, and the distances and angles observed in this study for such supramolecular interactions are comparable to the values reported for similar compounds. 32,48,49 Crystal structure analyses of PD series compounds In PD series compounds, a quinoline ring is linked to a PAH ring, such as naphthalene, anthracene, or pyrene, through ethylene linkage. Further, the hydroxyl group at the 8th position of the quinoline is sulfonated in these compounds.…”

“…2S-8HQs exhibit important pharmacological activities, including anticancer, anti-HIV-1, antimicrobial, antimalarial, and anti-Alzheimer activities. [31][32][33][34][35][36] By introducing suitable functional substituents on the styryl and quinoline rings, the properties of 2S-8HQs could be improved. There have been several attempts to develop novel anticancer agents by substituting the styryl part of the 2S-8HQs with other aromatic ring systems.…”

“…There have been several attempts to develop novel anticancer agents by substituting the styryl part of the 2S-8HQs with other aromatic ring systems. 32,37 However, substituting the styryl moiety of 2S-8HQs with a PAH moiety has rarely been attempted.…”