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 Cansen
Ergun, Sezen Guntekin
Hamel, Ernest
Cetin-Atalay, Rengul
Novel compounds containing polar and nonpolar substitutions on the prop-2-en-1-on linker of the trans-indol-3-ylacrylamide scaffold were designed by modeling within the colchicine site of tubulin and then synthesized to determine the role of such substitutions on tubulin polymerization. We first determined the in vitro antiproliferation activities of the compounds against cancer cell lines with a particular focus on hepatocellular carcinoma. The results indicated that five of the compounds showed moderate antitumor activities. When the tubulin polymerization inhibitory effect of these compounds was evaluated, compound 13 was determined to be a tubulin polymerization inhibitor. Furthermore, cell cycle analysis for compound 13 resulted in G2/M-phase arrest in Huh7 cells. The results indicated that polar substitutions on the indole acrylamide scaffold enhance potency against tubulin polymerization. However, the substitution-related bioactivity shifting was not observed on the cancer cell lines since the inhibition mechanisms of the compounds may vary.


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Adem, Umut; Özenbaş, Ahmet Macit; Department of Metallurgical and Materials Engineering (2003)
In this study, barium strontium titanate (BST) thin films with different compositions (Ba0.9Sr0.1TiO3, Ba0.8Sr0.2TiO3, Ba0.7Sr0.3TiO3, Ba0.5Sr0.5TiO3) were produced by chemical solution deposition technique. BST solutions were prepared by dissolving barium acetate, strontium acetate and titanium isopropoxide in acetic acid and adding ethylene glycol as a chelating agent and stabilizer to this solution, at molar ratio of acetic acid/ethylene glycol, 3:1. The solution was then coated on Si and Pt//Ti/SiO2/Si ...
Synthesis of Bishomoinositols and an Entry for Construction of a Substituted 3-Oxabicyclo[3.3.1]nonane Skeleton
BARAN, ARİF; Bekarlar, Merve; Aydin, Gokay; NEBİOĞLU, MEHMET; ŞAHİN, Ertan; Balcı, Metin (2012-02-03)
1,3,3a,7a-Tetrahydro-2-benzofuran was used as key compound for the synthesis of various bishomoinositol derivatives. The diene was subjected to an epoxidation reaction for further functionalization of the diene unit. The bisepoxide obtained was submitted to a ring-opening reaction with acid in the presence of water. Various bishomoinositols were synthesized. However, when the reaction was carried out in the presence of acetic anhydride, a substituted 3-oxabicyclo[3.3.1]nonane skeleton was formed. The mechan...
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Koyuncu, Zeynep; Hacaloğlu, Jale; Department of Chemistry (2009)
In this study, polymerization mechanisms of aromatic (C6H5 or C6F5) and alkyl (CH3, C2H5, C3H7, C6H13, C12H25 or C18H37) amine based naphthoxazine monomers (15-Na, 15Na-C1, 15Na-C2, 15Na-C3, 15Na-C6, 15Na-C12 and 15Na-C18) and thermal degradation mechanisms of polynaphthoxazines synthesized by curing the naphthoxazine monomers (P-15-Na, P-15NaF, P-15Na-C1, P-15Na-C2, P-15Na-C3, P-15Na-C6, P-15Na-C12 and P-15Na-C18) were studied by direct pyrolysis mass spectrometry. During the curing process, the evolutions...
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In this thesis, solid state reactions of Ln2O3, Y2O3, B2O3 and (NH4)2HPO4 were investigated to synthesize LnBP2O8 (Ln= Dy, Ho, Er) and YBP2O8 type of borophosphates which were not reported before. The products were analyzed by XRD, IR, DTA, SEM and EDX methods. In the first part of this thesis, synthesis of YBP2O8 through the solid state reaction of Y2O3 + 4(NH4)2HPO4 + B2O3 have been studied in the range 800-1140 °C. Orthophosphates of Dysprosium, Holmium, Erbium and Yttrium have tetragonal xenotime (YPO4)...
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In the current study, an in-situ oxidative polymerization method was used to synthesize polyaniline-coated tungsten trioxide biphasic composite (PANI@WO3). The as-developed composite material properties were elucidated using different characterization tools such as X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), N2 sorption-desorption isotherm, and X-ray photoelect...
Citation Formats
M. Hawash et al., “Design and synthesis of novel substituted indole-acrylamide derivatives and evaluation of their anti-cancer activity as potential tubulin-targeting agents,” JOURNAL OF MOLECULAR STRUCTURE, vol. 1254, pp. 0–0, 2022, Accessed: 00, 2022. [Online]. Available: