Novel Derivatives of 4,6‐Dihydroxy‐2‐Quinolone‐3‐Carboxamides as Potential PI3Kα Inhibitors

Sweidan, Kamal; Elfadel, Hussein; Sabbah, Dima A.; Bardaweel, Sanaa K.; Hajjo, Rima; Anjum, Shabana; Sinoj, Jithna; Nair, Vidhya A; Abu‐Gharbieh, Eman; El‐Huneidi, Waseem

doi:10.1002/slct.202202263

Cited by 4 publications

(1 citation statement)

References 71 publications

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“…Results demonstrated that two N-phenyl-6-chloro carboxamide analogues (q6, q7; Figure 3) exerted significant toxicity against human epithelial colorectal adenocarcinoma (Caco-2) and human colon cancer (HCT-116) cell lines. Furthermore, two 4,6-dihydroxy-2-quinolone-3-carboxamide derivatives (q8, q9; Figure 3) exhibited the most potent cytotoxic effect on breast cancer (MCF-7) and colon cancer (HCT-116) cell lines [39,40]. In 2020, Srigouri Huddara and his team introduced 4-hydroxy-2-oxo-1,2-dihydroquinolines as potential inhibitors of Streptococcus pneumoniae.…”

Section: Introductionmentioning

confidence: 99%

Novel Multi-Target Agents Based on the Privileged Structure of 4-Hydroxy-2-quinolinone

Kostopoulou,

Tzani,

Chronaki

et al. 2023

Molecules

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In this work, the privileged scaffold of 4-hydroxy-2quinolinone is investigated through the synthesis of carboxamides and hybrid derivatives, as well as through their bioactivity evaluation, focusing on the ability of the molecules to inhibit the soybean LOX, as an indication of their anti-inflammatory activity. Twenty-one quinolinone carboxamides, seven novel hybrid compounds consisting of the quinolinone moiety and selected cinnamic or benzoic acid derivatives, as well as three reverse amides are synthesized and classified as multi-target agents according to their LOX inhibitory and antioxidant activity. Among all the synthesized analogues, quinolinone–carboxamide compounds 3h and 3s, which are introduced for the first time in the literature, exhibited the best LOX inhibitory activity (IC50 = 10 μM). Furthermore, carboxamide 3g and quinolinone hybrid with acetylated ferulic acid 11e emerged as multi-target agents, revealing combined antioxidant and LOX inhibitory activity (3g: IC50 = 27.5 μM for LOX inhibition, 100% inhibition of lipid peroxidation, 67.7% ability to scavenge hydroxyl radicals and 72.4% in the ABTS radical cation decolorization assay; 11e: IC50 = 52 μM for LOX inhibition and 97% inhibition of lipid peroxidation). The in silico docking results revealed that the synthetic carboxamide analogues 3h and 3s and NDGA (the reference compound) bind at the same alternative binding site in a similar binding mode.

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Section: Introductionmentioning

confidence: 99%

Novel Multi-Target Agents Based on the Privileged Structure of 4-Hydroxy-2-quinolinone

Kostopoulou,

Tzani,

Chronaki

et al. 2023

Molecules

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Developing our knowledge of the quinolone scaffold and its value to anticancer drug design

Singh,

Bhatia,

Biharee

et al. 2023

Expert Opinion on Drug Discovery

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Quinolone Derivatives as Anticancer Agents: Importance in Medicinal Chemistry

Azzman,

Anwar,

Syazani Mohamed

et al. 2024

CTMC

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Abstract:: Quinolone is a heterocyclic compound containing carbonyl at the C-2 or C-4 positions with nitrogen at the C-1 position. The scaffold was first identified for its antibacterial properties, and the derivatives were known to possess many pharmacological activities, including anticancer. In this review, the quinolin-2(H)-one and quinolin-4(H)-one derivatives were identified to inhibit several various proteins and enzymes involved in cancer cell growth, such as topoisomerase, mi-crotubules, protein kinases, phosphoinositide 3-kinases (PI3K) and histone deacetylase (HDAC). Hybrids of quinolone with curcumin or chalcone, 2-phenylpyrroloquinolin-4-one and 4-quinolone derivatives have demonstrated strong potency against cancer cell lines. Additionally, quinolones have been explored as inhibitors of protein kinases, including EGFR and VEGFR. Therefore, this review aims to consolidate the medicinal chemistry of quinolone derivatives in the pipeline and discuss their similarities in terms of their pharmacokinetic profiles and potential target sites to provide an understanding of the structural requirements of anticancer quinolones.

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Novel Derivatives of 4,6‐Dihydroxy‐2‐Quinolone‐3‐Carboxamides as Potential PI3Kα Inhibitors

Cited by 4 publications

References 71 publications

Novel Multi-Target Agents Based on the Privileged Structure of 4-Hydroxy-2-quinolinone

Novel Multi-Target Agents Based on the Privileged Structure of 4-Hydroxy-2-quinolinone

Developing our knowledge of the quinolone scaffold and its value to anticancer drug design

Quinolone Derivatives as Anticancer Agents: Importance in Medicinal Chemistry

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