Design, synthesis and anticancer properties of IsoCombretaQuinolines as potent tubulin assembly inhibitors

Khelifi, Ilhem; Naret, Timothée; Renko, Dolor; Hamzé, Abdallah; Bernadat, Guillaume; Bignon, Jérôme; Lenoir, C.; Dubois, Joëlle; Brion, Jean‐Daniel; Provot, Olivier; Alami, Mouâd

doi:10.1016/j.ejmech.2016.11.012

Cited by 73 publications

(53 citation statements)

References 41 publications

(37 reference statements)

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“…Accordingly, the same quinoline‐like system occurred in some of the previously reported 31 compounds . Incidentally, quinoline derivatives were also reported by Shobeiri and Khelifi as potential CBSIs based on experimental evidences. Only 1,2,4‐triazole derivative 16 belongs to the group IV .…”

Section: Resultssupporting

confidence: 85%

Automated identification of structurally heterogeneous and patentable antiproliferative hits as potential tubulin inhibitors

et al. 2018

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By employing a recently developed hierarchical computational platform, we identified 37 novel and structurally diverse tubulin targeting compounds. In particular, hierarchical molecular filters, based on molecular shape similarity, structure-based pharmacophore, and molecular docking, were applied on a large chemical collection of commercial compounds to identify unexplored and patentable microtubule-destabilizing candidates. The herein proposed 37 novel hits, showing new molecular scaffolds (such as 1,3,3a,4-tetraaza-1,2,3,4,5,6,7,7a-octahydroindene or dihydropyrrolidin-2-one fused to a chromen-4-one), are provided with antiproliferative activity in the μm range toward MCF-7 (human breast cancer lines). Importantly, there is a likely causative relationship between cytotoxicity and the inhibition of tubulin polymerization at the colchicine binding site, assessed through fluorescence polymerization assays.

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Section: Resultssupporting

confidence: 85%

Automated identification of structurally heterogeneous and patentable antiproliferative hits as potential tubulin inhibitors

et al. 2018

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“…

Novel quinoline derivatives carrying nitrones and oxime as nitric oxide donors were prepared and characterized using different spectroscopic techniques. Several mechanisms can explain the anticancer effect of quinoline derivatives including: topoisomerase inhibition, [21][22][23] DNA intercalation, [24] protein kinases inhibition, [25][26][27] tubulin polymerase inhibition, [28][29][30][31] and induction of apoptosis. Antiproliferative screening results showed that the 2-benzylthioquinoline nitrones 6e and 6f and the 2-methylthio analogues 6g and 6h exhibited promising antiproliferative activity especially against leukemia and colon cancer cell lines.

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confidence: 99%

“…Antiproliferative screening results showed that the 2-benzylthioquinoline nitrones 6e and 6f and the 2-methylthio analogues 6g and 6h exhibited promising antiproliferative activity especially against leukemia and colon cancer cell lines. [31] Compound II exhibits remarkable anticancer activity against HL60 cancer cell line with IC 50 of 0.68 μM (Figure 1). A remarkable overexpression of caspase-3 protein levels was observed in cells treated with the tested compounds.…”

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confidence: 99%

“…[32,33] Quinoline derivative I exhibited potent anticancer activity against brain cancer cell line U87 with IC 50 of 1.5 nM. [31] Compound II exhibits remarkable anticancer activity against HL60 cancer cell line with IC 50 of 0.68 μM (Figure 1). [33] Incorporation of biologically active moieties into quinoline such as nitrones [34] and oximes [35] may produce biologically active anticancer agents.…”

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confidence: 99%

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Novel quinoline derivatives carrying nitrones/oximes nitric oxide donors: Design, synthesis, antiproliferative and caspase-3 activation activities

Abdelbaset

Abdel‐Aziz

Abuo‐Rahma

et al. 2018

Arch. Pharm. Chem. Life Sci.

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Novel quinoline derivatives carrying nitrones and oxime as nitric oxide donors were prepared and characterized using different spectroscopic techniques. Nitrones can release nitric oxide in larger amounts compared to corresponding oximes. Antiproliferative screening results showed that the 2-benzylthioquinoline nitrones 6e and 6f and the 2-methylthio analogues 6g and 6h exhibited promising antiproliferative activity especially against leukemia and colon cancer cell lines. Compounds 6c, 6e, and 6f exhibited higher potency as anticancer agents compared to doxorubicin, with IC 50 ranging from 0.45 to 0.91 μM. A remarkable overexpression of caspase-3 protein levels was observed in cells treated with the tested compounds. Compound 6e exhibited more pre-G1 apoptosis and cell cycle arrest at the G2/M phase than in other phases.These results revealed that the tested compounds can cause programmed cell death through overexpression of caspase 3, which may be attributed to the release of nitric oxide. K E Y W O R D S antiproliferative, apoptosis, caspase 3, nitric oxide, nitrones, oximes 1 | INTRODUCTION Quinoline is a significant nucleus which has attracted the attention of medicinal chemists due to its variable pharmacological activities. Easy functionalization of various ring positions of quinoline makes it an attractive synthetic building block for design and synthesis of new drugs. Additionally, quinolines are considered as an interesting group of compounds, many of which have widespread pharmacologicalactions such as anti-microbial, [1][2][3][4] anti-inflammatory, [5][6][7][8] antitubercular, [9][10][11][12] anti-convulsant, [13] antihypertensive, [14,15] antioxidant, [16][17][18][19] and anticancer [20] activities. Several mechanisms can explain the anticancer effect of quinoline derivatives including: topoisomerase inhibition, [21][22][23] DNA intercalation, [24] protein kinases inhibition, [25][26][27] tubulin polymerase inhibition, [28][29][30][31] and induction of apoptosis. [32,33] Quinoline derivative I exhibited potent anticancer activity against brain cancer cell line U87 with IC 50 of 1.5 nM. [31] Compound II exhibits remarkable anticancer activity against HL60 cancer cell line with IC 50 of 0.68 μM (Figure 1). [33] Incorporation of biologically active moieties into quinoline such as nitrones [34] and oximes [35] may produce biologically active anticancer agents.Compound III showed significant anticancer activity with IC 50 of 31.42 μM against Hep-G 2 cancer cell line (Figure 1). [34] Nitrones are a Arch Pharm Chem Life Sci. 2019;352:e1800270.wileyonlinelibrary.com/journal/ardp

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“…The use of the quinoline moiety is based on work by Khelifi et al in which a quinoline structure was predicted by docking studies to form a hydrogen bond with Cys-241 residue of the CBS through the N-1 atom of the quinoline ring. Quinoline 48 (Figure 7) displayed nano-and sub-nanomolar levels of cytotoxicity against five cancer cell lines and inhibited tubulin polymerization with micromolar IC 50 values [105].…”

Section: Quinoline and Indole Derivatives Of Isoca-4mentioning

confidence: 99%

Colchicine-Binding Site Inhibitors from Chemistry to Clinic: A Review

2020

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It is over 50 years since the discovery of microtubules, and they have become one of the most important drug targets for anti-cancer therapies. Microtubules are predominantly composed of the protein tubulin, which contains a number of different binding sites for small-molecule drugs. There is continued interest in drug development for compounds targeting the colchicine-binding site of tubulin, termed colchicine-binding site inhibitors (CBSIs). This review highlights CBSIs discovered through diverse sources: from natural compounds, rational design, serendipitously and via high-throughput screening. We provide an update on CBSIs reported in the past three years and discuss the clinical status of CBSIs. It is likely that efforts will continue to develop CBSIs for a diverse set of cancers, and this review provides a timely update on recent developments.

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Design, synthesis and anticancer properties of IsoCombretaQuinolines as potent tubulin assembly inhibitors

Cited by 73 publications

References 41 publications

Automated identification of structurally heterogeneous and patentable antiproliferative hits as potential tubulin inhibitors

Automated identification of structurally heterogeneous and patentable antiproliferative hits as potential tubulin inhibitors

Novel quinoline derivatives carrying nitrones/oximes nitric oxide donors: Design, synthesis, antiproliferative and caspase-3 activation activities

Colchicine-Binding Site Inhibitors from Chemistry to Clinic: A Review

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