Design and synthesis of novel substituted indole-acrylamide derivatives and evaluation of their anti-cancer activity as potential tubulin-targeting agents

Hawash, Mohammed; Kahraman, Deniz; Olğaç, Abdurrahman; Ergün, Sezen Güntekin; Hamel, Ernest; Çetin-Atalay, Rengül; Baytas, Sultan Nacak

doi:10.1016/j.molstruc.2022.132345

Cited by 24 publications

(17 citation statements)

References 30 publications

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“…After that, each aniline derivative (1.8 mmol) was added individually and the mixture was allowed to stir for 72 h. Re-crystallization and flash chromatography was used to purify the final products, and all compounds were characterized by using HRMS and proton NMR to confirm their structures. The synthesis of these compounds is presented 13 , 24 in Fig. 2 .…”

Section: Methodsmentioning

confidence: 99%

In vitro and in vivo assessment of the antioxidant potential of isoxazole derivatives

Hawash

Jaradat

Abualhasan

et al. 2022

Sci Rep

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Previously developed fluorophenyl-isoxazole-carboxamides derivatives were re-synthesized and their scavenging activity against DPPH free radical and inhibitory activity against lipase and α-amylase enzymes were evaluated. The inhibition of the tested enzymes was weak while the most potent activities were observed in the DPPH assay. In particular, compounds 2a and 2c demonstrated high antioxidant potency with IC50 values of 0.45 ± 0.21 and 0.47 ± 0.33 µg/ml, respectively, when compared to Trolox, the positive control compound, which has an IC50 value of 3.10 ± 0.92 µg/ml. Based on the in vitro results, the most potent compound 2a was chosen for in vivo evaluation of antioxidant properties using 20 male mice injected intra-peritoneally and divided into four groups. The in vivo results revealed that total antioxidant capacity (TAC) obtained for mice treated with 2a was two folds greater than that of mice treated with the positive control Quercetin. Although further biological and preclinical investigations need to be performed to assess the therapeutic potential of 2a, the results of this study show promising antioxidant activities both in vitro and in vivo.

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Section: Methodsmentioning

confidence: 99%

In vitro and in vivo assessment of the antioxidant potential of isoxazole derivatives

Hawash

Jaradat

Abualhasan

et al. 2022

Sci Rep

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“…The same group of researchers tried to target the tubulin by adding various substituents, such as methyl, nitrile, carboxylic acid, and ester, to the linker of St.32. However, the derivative with the nitrile group was considered as a tubulin polymerization inhibitor [ 94 ]. Another novel series of indole-based oxalamide was developed and designed, amongst which St.33 ( Figure 7 ) exhibits potent anticancer activities against HeLa, PC-3, and HCT-116 cancer cell lines.…”

Section: Indole Analoguesmentioning

confidence: 99%

Recent Advances of Tubulin Inhibitors Targeting the Colchicine Binding Site for Cancer Therapy

Hawash

2022

Biomolecules

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Cancer accounts for numerous deaths each year, and it is one of the most common causes of death worldwide, despite many breakthroughs in the discovery of novel anticancer candidates. Each new year the FDA approves the use of new drugs for cancer treatments. In the last years, the biological targets of anticancer agents have started to be clearer and one of these main targets is tubulin protein; this protein plays an essential role in cell division, as well as in intracellular transportation. The inhibition of microtubule formation by targeting tubulin protein induces cell death by apoptosis. In the last years, numerous novel structures were designed and synthesized to target tubulin, and this can be achieved by inhibiting the polymerization or depolymerization of the microtubules. In this review article, recent novel compounds that have antiproliferation activities against a panel of cancer cell lines that target tubulin are explored in detail. This review article emphasizes the recent developments of tubulin inhibitors, with insights into their antiproliferative and anti-tubulin activities. A full literature review shows that tubulin inhibitors are associated with properties in the inhibition of cancer cell line viability, inducing apoptosis, and good binding interaction with the colchicine binding site of tubulin. Furthermore, some drugs, such as cabazitaxel and fosbretabulin, have been approved by FDA in the last three years as tubulin inhibitors. The design and development of efficient tubulin inhibitors is progressively becoming a credible solution in treating many species of cancers.

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“…Several 1,8-Naphthyridine derivatives have gained the attention of researchers for their anticancer properties and SAR studies on their efficacy as antitumor active compounds have been reported [21]. Furthermore, many other heterocyclic compounds such as indole, furano, isoxazole derivatives characterized by a carboxamide substituent have shown interesting anti-proliferative activity against different cancer cell lines [22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and In Vitro Characterization of Selective Cannabinoid CB2 Receptor Agonists: Biological Evaluation against Neuroblastoma Cancer Cells

et al. 2022

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1,8-naphthyridine-3-carboxamide structures were previously identified as a promising scaffold from which to obtain CB2R agonists with anticancer and anti-inflammatory activity. This work describes the synthesis and functional characterization of new 1,8-naphthyridin-2(1H)-one-3-carboxamides with high affinity and selectivity for CB2R. The new compounds were able to pharmacologically modulate the cAMP response without modulating CB2R-dependent β-arrestin2 recruitment. These structures were also evaluated for their anti-cancer activity against SH-SY5Y and SK-N-BE cells. They were able to reduce the cell viability of both neuroblastoma cancer cell lines with micromolar potency (IC50 of FG158a = 11.8 μM and FG160a = 13.2 μM in SH-SY5Y cells) by a CB2R-mediated mechanism. Finally, in SH-SY5Y cells one of the newly synthesized compounds, FG158a, was able to modulate ERK1/2 expression by a CB2R-mediated effect, thus suggesting that this signaling pathway might be involved in its potential anti-cancer effect.

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Design and synthesis of novel substituted indole-acrylamide derivatives and evaluation of their anti-cancer activity as potential tubulin-targeting agents

Cited by 24 publications

References 30 publications

In vitro and in vivo assessment of the antioxidant potential of isoxazole derivatives

In vitro and in vivo assessment of the antioxidant potential of isoxazole derivatives

Recent Advances of Tubulin Inhibitors Targeting the Colchicine Binding Site for Cancer Therapy

Synthesis and In Vitro Characterization of Selective Cannabinoid CB2 Receptor Agonists: Biological Evaluation against Neuroblastoma Cancer Cells

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