Two Important Anticancer Mechanisms of Natural and Synthetic Chalcones

Abstract

ATP-binding cassette subfamily G and tubulin pharmacological mechanisms decrease the effectiveness of anticancer drugs by modulating drug absorption and by creating tubulin assembly through polymerization. A series of natural and synthetic chalcones have been reported to have very good anticancer activity, with a half-maximal inhibitory concentration lower than 1 µM. By modulation, it is observed in case of the first mechanism that methoxy substituents on the aromatic cycle of acetophenone residue and substitution of phenyl nucleus by a heterocycle and by methoxy or hydroxyl groups have a positive impact. To inhibit tubulin, compounds bind to colchicine binding site. Presence of methoxy groups, amino groups or heterocyclic substituents increase activity.

(E)-2-Benzylidenecyclanones: Part XVIII.[1] Study the Possible Link Between Glutathione Reactivity and Cancer Cell Cytotoxic Effects of Some Cyclic Chalcone Analogs. A Comparison of the Reactivity of the Open-Chain and the Seven-Membered Homologs

“…The present results do not indicate a direct correlation with the cancer cell cytotoxicity of the two derivatives, which are of two orders of magnitude different against most of the investigated cell lines. The anticancer potential of chalcones is correlated with their ability to act on various molecular targets such as ABCG2, tubulin, activated nuclear B cell growth (NF-κB), vascular endothelial growth factor (VEGF), tyrosine kinase receptor (EGFR), mesenchymal-epithelial transition factor (MET), 5-α reductase, ACP-reductase, histone deacetylase, p53, CDC25B (protein tyrosine phosphatase), retinoic acid receptors, estrogenic topoisomerase receptors and MDM2 [9]. Considering the present and our previous results [10][11][12][13][14][15][16], it is reasonable to suppose that the molecular basis of the different biological effects of IIb and IIc is related to the non-covalent interactions of the compounds [49].…”

“…The kOH rate constants were calculated for chalcone compounds, and the results indicate that the compounds with the highest kOH values point to greater reactivity. The order of reactivity potential was observed as CH3SH (9.15×10 9 x M −1 s −1 ) Ia (9.01×10 9 x M −1 s −1 ) > IIa (7.85×10 9 x M −1 s −1 ) > CH3S -(5.48×10 9 x M −1 s −1 ).…”

“…Because of the wide range of beneficial biological actions of the natural chalcones, several analogs have been syn-thesized andamong others -tested for their antioxidant, antimicrobial, antiprotozo-al, antiulcer, antihistaminic, antidiabetic, anti-inflammatory, anticancer and also neu-roprotective activities [3][4][5][6]. The molecular mechanisms of the published biologi-cal/pharmacological effects can be associated with their (a) non-covalent interactions with biological macromolecules and (b) covalent modification of preferably the soft nucleophilic thiol function(s) of amino acids, peptides, and proteins [7][8][9].…”

Cellular Mechanistic Considerations on Cytotoxic Mode of Action of Phosphino Ru(II) and Ir(III) Complexes

“…[23,[26][27][28] Moreover, cancer cells acquire resistance to antitumor chemotherapy by mutations in the process of carcinogenesis or initiate it to many conventional chemotherapeutic agents. [54][55][56] Thus, it is a common strategy to modify the chemical structures of biologically active compounds to increase their anti-proliferative properties. [36,54,55,57] For instance, research on polymethoxy substitutes analogs of resveratrol, a trihydroxy stilbene derivative commonly used as an antioxidant and for its antiinflammatory effects, [58,59] shows more potency of anti-tumor and anti-inflammatory activity than resveratrol by downregulating cyclooxygenase 2 (COX-2) and inducing apoptosis with lower concentration.…”

“…[54][55][56] Thus, it is a common strategy to modify the chemical structures of biologically active compounds to increase their anti-proliferative properties. [36,54,55,57] For instance, research on polymethoxy substitutes analogs of resveratrol, a trihydroxy stilbene derivative commonly used as an antioxidant and for its antiinflammatory effects, [58,59] shows more potency of anti-tumor and anti-inflammatory activity than resveratrol by downregulating cyclooxygenase 2 (COX-2) and inducing apoptosis with lower concentration. [57] Another study presents methoxychalcones, where the presence of methoxy group can either inhibit tubulin polymerization or ABCG2 (breast cancer resistance protein) activity, depending on the location of this substituent.…”