Cytotoxic effect and molecular docking of 4-ethoxycarbonylmethyl-1-(piperidin-4-ylcarbonyl)-thiosemicarbazide—a novel topoisomerase II inhibitor

Abstract

The preliminary cytotoxic effect of 4-ethoxycarbonylmethyl-1-(piperidin-4-ylcarbonyl)-thiosemicarbazide hydrochloride (1)—a potent topoisomerase II inhibitor—was measured using a MTT assay. It was found that the compound decreased the number of viable cells in both estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB-231breast cancer cells, with IC50 values of 146 ± 2 and 132 ± 2 μM, respectively. To clarify the molecular basis of the inhibitory action of 1, molecular docking studies were carried out. The results suggest that 1 targets the ATP binding pocket.Figure4-ethoxycarbonylmethyl-1-(piperidin-4-ylcarbonyl)-thiosemicarbazide hydrochlorideElectronic supplementary materialThe online version of this article (doi:10.1007/s00894-012-1679-6) contains supplementary material, which is available to authorized users.

Molecular Simulation of Nicotine-Related Alkaloids Interaction with Human DNA

“…Some of the diseases that go over the agenda in discussions on these issues are related to DNA deformation and mutations which can cause cancer. [6][7][8] It is currently known that cigarette use is directly related to lung, esophageal and skin cancers, as well as it can be related to heart disease. These findings let us worried even more when some statistics on the use of tobacco (Nicotiana tabacum) are analyzed.…”

Synthesis and Anticancer Activity of Tolmetin Thiosemicarbazides

“…Duffy and co-workers evaluated that tolmetin and other (NSAID)s have effects on increasing the cytotoxic activity of the anti-cancer drugs (3). Thiosemicarbazides, which are intermediate products of the synthesis for bioactive heterocyclic compounds, have taken attention of the researchers because of their clinical use and diverse biological activities (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) (Fig 1). In this work, we synthesized novel ten tolmetin thiosemicarbazide derivatives (4a-j) and investigated their anticancer activity against cancer cell lines.…”

New Heterocyclic Compounds from 1,2,4-triazoles Class with Potential Cytotoxic Activity

“…Due to its synthetic and biological versatility, investigations on compounds containing hydrazincarbothioamide groups have become attractive, targeting compounds for new drug development, because of their potentially biological activities involving antiproliferative activities [7,8]. Siwek and his collaborators have studied the antitumor action upon certain MCF-7 cell lines involved in breast cancer, upon certain substituted hydrazinecarbothioamides [7]. This property is due to their inhibitory action upon II and IV topoisomerase, an enzyme involved in DNA replication and cell transcription [8].…”

“…Compounds with dibenzo[a,d] [7]annulene moieties have many pharmacological applications: psychotropic action, antidepressant action, analgesic, anti-inflammatory, antihistamine action, anticonvulsant action, antimicrobial, antihypertensive, antiarrhythmic, antitumor, antiparasitic, inhibition of metallo-proteases activity etc [15][16][17][18][19].…”

“…Considering these aspects, this present work aims at making a synthesis between two different classes of compounds, hydrazinecarbothioamide derivatives and respectively 1,2,4-triazole derivatives with dibenzo [a,d] [7]annulene moieties and evaluation of the cytotoxic effect of new compounds.…”