Abstract
A small library of novel quinoline-3-carbaldehyde hydrazones (Series 1), acylhydrazones (Series 2), and arylsulfonylhydrazones (Series 3) bearing either a 1,2,4-triazole or benzotriazole ring at position 2 was prepared, characterized by elemental analyses and IR, NMR, and MS spectra, and then subjected to in vitro cytotoxicity studies on three human tumor cell lines: DAN-G, LCLC-103H, and SISO. In general, compounds 4, 6, and 8 substituted with a 1,2,4-triazole ring proved to be inactive, whereas the benzotriazole-containing quinolines 5, 7, and 9 elicited pronounced cancer cell growth inhibitory effects with IC50 values in the range of 1.23–7.39 µM. The most potent 2-(1H-benzotriazol-1-yl)-3-[2-(pyridin-2-yl)hydrazonomethyl]quinoline (5e) showed a cytostatic effect on the cancer cell lines, whereas N′-[(2-(1H-benzotriazol-1-yl)quinolin-3-yl)methylene]-benzohydrazide (7a) and N′-[(2-1H-benzotriazol-1-yl)quinolin-3-yl)methylene]-naphthalene-2-sulfonohydrazide (9h) exhibited selective activity against the pancreas cancer DAN-G and cervical cancer SISO cell lines. Based on the determined IC50 values, the compound 5e seems to be leading compound for further development as anticancer agent.
Highlights
The term “privileged structures” was coined by Evans and co-workers [1] and since has proven to be an effective approach in drug discovery process [2,3]
The quinoline ring is utilized in clinically used anticancer drugs, such as camptothecin and its analogues, e.g., topotecan, which are known as topoisomerase inhibitors [9,10] or multitarget kinase inhibitors, including lenvatinib and cabozantib [9], whereas omipalisib and dactolisib are currently under clinical trials as agents targeting the phosphoinositide 3-kinase (PI3K) [9]
Our research started with reactions of 2-chloroquinoline-3-carbaldehyde (1) [31,32] with
Summary
The term “privileged structures” was coined by Evans and co-workers [1] and since has proven to be an effective approach in drug discovery process [2,3]. The quinoline ring is utilized in clinically used anticancer drugs, such as camptothecin and its analogues, e.g., topotecan, which are known as topoisomerase inhibitors [9,10] or multitarget kinase inhibitors, including lenvatinib and cabozantib [9], whereas omipalisib and dactolisib are currently under clinical trials as agents targeting the phosphoinositide 3-kinase (PI3K) [9] It is worth noting, that the antiproliferative effects of the quinoline-containing compounds may result from cell cycle arrest [11,12,13,14,15], apoptosis [16,17], DNA intercalation [18,19], inhibition of angiogenesis [20,21,22], inhibition of proteasome [23,24], and disruption of tubulin polymerization [25,26].
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