Naphthoquinone-based Hydrazone Hybrids: Synthesis and Potent Activity Against Cancer Cell Lines

Abstract

Background: Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also compounds with acute cytotoxicity, immunotoxicity, carcinogenesis, and cardio- and hepatotoxicity, then the modification at their redox center is an interesting strategy to overcome such harmful activity. Objective: In this study, four novel semisynthetic hydrazones, derived from the isomers α- and β-lapachones (α and β, respectively) and coupled with the drugs hydralazine (HDZ) and isoniazid (ACIL), were prepared, evaluated by electrochemical methods and assayed for anticancer activity. Method: The semisynthetic hydrazones were obtained and had their molecular structures established by NMR, IR, and MS. Anticancer activity was evaluated by cell viability determined by reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The electrochemical studies, mainly cyclic voltammetry, were performed, in aprotic and protic media. Result: The study showed that the compounds 2, 3, and 4 were active against at least one of the cancer cell lines evaluated, being compounds 3 and 4 the most cytotoxic. Toward HL-60 cells, compound 3 was 20x more active than β-lapachone, and 3x more cytotoxic than doxorubicin. Furthermore, 3 showed an SI value of 39.62 for HL-60 cells. Compound 4 was active against all cancer cells tested, with IC50 values in the range 2.90–12.40 μM. Electrochemical studies revealed a profile typical of self-protonation and reductive cleavage, dependent on the supporting electrolyte. Conclusion: These results therefore indicate that compounds 3 and 4 are strong candidates as prototypes of new antineoplastic drugs.

Chalcone Derivatives: Role in Anticancer Therapy

“…In addition to the aforementioned chalcone hybrids, other hybrids, such as chalcone–ferrocene [ 95 , 96 , 97 ], chalcone–furan/thiophene hybrids [ 98 , 99 , 100 , 101 ], chalcone–pyridine/pyrimidine hybrids [ 102 , 103 , 104 , 105 , 106 ], chalcone–quinoline/quinolone hybrids [ 107 , 108 , 109 , 110 , 111 ], chalcone–quinoxaline/quinazolinone hybrids [ 112 , 113 , 114 ], chalcone-quinone hybrids [ 115 , 116 , 117 ], chalcone–triazine hybrids [ 118 , 119 ], and chalcone–dithiocarbamate hybrids [ 120 , 121 ] also showed certain anticancer activity.…”

New Metal(II) Complexes of 2-Hydroxy-N-(2-Hydroxynaph Thalene-1-yl) Methylene Benzohydrazide: Synthesis and Spectroscopic Studies

“…It was concluded that its coordinate from measured the molar conductivity of the prepared complex solutions, as well as based on magnetic and electronic spectra measurements of the prepared complexes. (33,34) Table (2) shows the most important bands of prepared of ligand and complexes ( ‫لعدد‬ ‫ا‬ ، 1 ‫لسنة‬ ،) Magnetic susceptibility measurements were carried out at 25°C using Gouy method. The prepared Co (II) tetra coordinate complex showed the value of the magnetic moment (4.32 B.M), where the cobalt ion (II) in the 3d 7 system has three unpaired electrons, which is higher than the theoretical value (3.87B.M) due to the presence of the second orbital contribution, and this is consistent with the value of the moment magnetic Co(II) with tetrahedral structure.…”

“…Hydrazones are an important class of organic compounds (1) and they are azomethine compounds that contain the reactive structural unit (2) azomethine ( C=N-N) (3) . These compounds have basic properties due to the presence of the pair electrons on the nitrogen atom, as well as the double bond of the azomethine group (4) .…”

Synthesis and antileishmanial activity of naphthoquinone-based hybrids

“…For the synthesis, all the reagents used were obtained from commercial sources and used without prior purification, with the exception of hydralazine hydrochloride, which was obtained from Apresolina ® pills (Anovis Industrial Farmacêutica Ltda) [10,13]. The synthesized substances had its melting temperatures determined in triplicate using analog fusiometer, model PFM-II (MS Tecnopon ® instrumentation).…”