Abstract
A series of new quinoline derivatives (6-phenyl-6H-chromeno, [4,3-b] quinoline) have been prepared by using 4-chloro-2-phenyl-2H-chromene-3-carbaldehyde and various substituted nitroarenes as starting materials in the presence of Tin (II) chloride dihydrate and ethanol. The conversion in this synthesis involves the following steps (i) reduction of nitroarenes to anilines, (ii) Coupling of the anilines, chromene aldehydes (iii) Cyclization of resulting species and (iv) dehydration of cyclic intermediates. Several new quinolones have been prepared. We screened eight compounds of this novel series (6a-r) in three different cancer cell lines (B16F10, MCF7 and A549). The screened compounds showed moderate anticancer activity on two of the studied cell lines with best IC50 values of compound 6i (6.10±1.23 µM) and 6m (8.21±2.31 µM) on MCF7 cells. The selected compounds 6i and 6m led to morphological changes after treatment on MCF7 cell line. Interestingly, detailed studies suggested that the compounds 6i and 6m induced apoptosis in MCF7 cells in an oxidative stress independent manner without causing necrosis. In addition, we found destabilization of mitochondrial membrane potential behind the observed anticancer activity. Our results clearly indicate the promising anticancer potential of this novel series. This method is operationally simple and works with a diverse range of substrates.
Highlights
The use of privileged structures in drug discovery has proven to be an effective strategy, allowing the generation of innovative hits/leads and successful optimization processes, (Musiol et al, 2017) Chromene and Quinolines are recognized as a privileged structures and useful templates for the design of novel compounds with potential pharmacological interest (Fig. 1), (Fernanda et al, 2017, Fernanda et al, 2014) Undoubtedly, quinoline-based compounds have a remarkable impact on anticancer drugs
Various quinoline derivatives exhibit a broad range of pharmacological properties such as anti-cancer, (Peczynska-Czoch, 1999), (Connie, 1995) anti-tuberculosis, (Singh, 2004) anti-hypertensive, (Leonard, 2004) anti-HIV, (Nevinsky, 1999) and anti-alzheimer activities. (Luque, 2001) Substituted quinolones function as antagonists for 5HT3, NK-3, endothelin and leukotriene receptors. (Pinto et al, 1995) They are utilized as intermediates for the design of bio-potent molecules. (Cuny et al, 2000)
The ability to create carbon-carbon carbon-nitrogen bonds is at the heart of organic synthesis, heterogeneous catalytic processes are apt at creating such bonds, especially in reductive amination or relay sequences where more one bond is formed allowing for rapid assembly of complex structures
Summary
The use of privileged structures in drug discovery has proven to be an effective strategy, allowing the generation of innovative hits/leads and successful optimization processes, (Musiol et al, 2017) Chromene and Quinolines are recognized as a privileged structures and useful templates for the design of novel compounds with potential pharmacological interest (Fig. 1), (Fernanda et al, 2017, Fernanda et al, 2014) Undoubtedly, quinoline-based compounds have a remarkable impact on anticancer drugs. The quinoline moiety offers a accessible, well-understood scaffold for designing new drugs. It is a very potent molecule with the druggability for structure optimization through established synthetic pathways. For these reasons, quinoline-core anticancer drugs have a strong position in modern medicinal chemistry. (Musiol et al, 2017) Quinolines and Chromenes are frequently found structural units in biologically potent natural products, (Michael 2005) in particular, alkaloids. Various quinoline derivatives exhibit a broad range of pharmacological properties such as anti-cancer, (Peczynska-Czoch, 1999), (Connie, 1995) anti-tuberculosis, (Singh, 2004) anti-hypertensive, (Leonard, 2004) anti-HIV, (Nevinsky, 1999) and anti-alzheimer activities. Various quinoline derivatives exhibit a broad range of pharmacological properties such as anti-cancer, (Peczynska-Czoch, 1999), (Connie, 1995) anti-tuberculosis, (Singh, 2004) anti-hypertensive, (Leonard, 2004) anti-HIV, (Nevinsky, 1999) and anti-alzheimer activities. (Luque, 2001) Substituted quinolones function as antagonists for 5HT3, NK-3, endothelin and leukotriene receptors. (Pinto et al, 1995) They are utilized as intermediates for the design of bio-potent molecules. (Cuny et al, 2000)
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