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

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 −NO2 groups at the eighthposition
of the quinoline ring and −SCH3, −OCH3, 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 −NO2 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 −NO2 substituent. Similarly, the electron-withdrawing group −Br
on the styryl ring enhanced the cytotoxicity in both series. The IC50 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
IC50 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.