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PubMed2004

Syntheses, crystal structures and antimicrobial activities of monomeric 8-coordinate, and dimeric and monomeric 7-coordinate bismuth(III) complexes with tridentate and pentadentate thiosemicarbazones and pentadentate semicarbazone ligands.

Novel bismuth(III) complexes 1-4 with the tridentate thiosemicarbazone ligand of 2N1S donor atoms [Hmtsc (L1); 2-acetylpyridine (4N-morpholyl thiosemicarbazone)], the pentadentate double-armed thiosemicarbazone ligand of 3N2S donor atoms [H2dmtsc (L3); 2,6-diacetylpyridine bis(4N-morpholyl thiosemicarbazone)] and the pentadentate double-armed semicarbazone ligand of 3N2O donor atoms [H2dasc (L4b); 2,6-diacetylpyridine bis(semicarbazone)], were prepared by reactions of bismuth(III) nitrate or bismuth(III) chloride and characterized by elemental analysis, thermogravimetric and differential thermal analysis (TG/DTA), FTIR and NMR (1H and 13C) spectroscopy. The crystal and molecular structures of complexes 1, 2a, 2b and 4b, and the "free" ligand L1 were determined by single-crystal X-ray structure analysis. The dimeric 7-coordinate bismuth(III) complex [Bi(dmtsc)(NO3)]2, 1, and the monomeric 7-coordinate complexes [Bi(Hdasc)(H2O)](NO3)2.H2O (major product), 2a, and [Bi(dasc)(H2O)]NO3.H2O (minor product), 2b, all with pentagonal bipyramidal bismuth(III) centers, are depicted with one electron pair (6s2) of the bismuth(III) atom, deprotonated forms of multidentate thiosemicarbazone or semicarbazone ligands, and monodentate NO3 or H2O ligands, respectively. These complexes are related to the positional isomers of one electron pair of the bismuth(III) atom; 1 has an electron pair positioned in the pentagonal plane (basal position), while 2a and 2b have an electron pair in the apical position. The monomeric 8-coordinate complex [Bi(mtsc)2(NO3)], 4b, which was obtained by slow evaporation in MeOH of the 1.5 hydrates 4a, was depicted with one electron pair of the bismuth(III) atom, two deprotonated mtsc- ligand and one nitrate ion. On the other hand, crystals of the complex "[Bi(mtsc)Cl2]", 3, prepared by a reaction of BiCl3 with L1 showed several polymorphs (3a, 3b, 3c and 3d) due to coordination and/or solvation of dimethyl sulfoxide (DMSO) used in the crystallization. Bismuth(III) complexes 1 and 4a showed selective and effective antibacterial activities against Gram-positive bacteria. The structure-activity relationship was discussed.

Anti-Bacterial Agents↗
PubMed1992

Synthesis and antitumor activity of 3- and 5-hydroxy-4-methylpyridine-2-carboxaldehyde thiosemicarbazones.

To develop an alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazone with clinical utility as an anticancer agent, two analogues, 3-hydroxy-4-methylpyridine-2-carboxaldehyde thiosemicarbazone (3-HMP) and 5-hydroxy-4-methylpyridine-2-carboxaldehyde thiosemicarbazone (5-HMP), of 5-hydroxypyridine-2-carboxaldehyde thiosemicarbazone (5-HP) have been designed and synthesized by two different methods. 3-HMP and 5-HMP both showed better antitumor activity than their respective parent compounds, 3-hydroxypyridine-2-carboxaldehyde thiosemicarbazone and 5-HP, in mice bearing the L1210 leukemia.

Animals↗
PubMed1992

Synthesis and antitumor activity of amino derivatives of pyridine-2-carboxaldehyde thiosemicarbazone.

Various substituted pyridine-2-carboxaldehyde thiosemicarbazones (12 compounds) have been synthesized and evaluated for antineoplastic activity in mice bearing the L1210 leukemia. Oxidation of 3-nitro-2-picoline,5-nitro-2-picoline,3-nitro-2,4-lutidine, and 5-nitro-2,4-lutidine with selenium dioxide was employed to generate the corresponding pyridine-2-carboxaldehydes, which were then converted to cyclic ethylene acetals and subsequently reduced to amino and hydroxyamino derivatives by catalytic hydrogenation. Condensation of nitro aldehydes and acetals with thiosemicarbazide afforded the respective thiosemicarbazones. Acetylation of the amino acetals and alkylsulfonation of the 5-amino acetal, followed by condensation with thiosemicarbazide was employed to yield amide thiosemicarbazones. The most active compounds synthesized were 3-aminopyridine-2-carboxaldehyde thiosemicarbazone and 3-amino-4-methylpyridine-2-carboxaldehyde thiosemicarbazone which produced against the L1210 leukemia, % T/C values of 246 and 255, and 40% 60-day long-term survivors at two daily doses of 40 mg/kg and 10 mg/kg, respectively, for six consecutive days.

Animals↗
PubMed1979

Comparative cytotoxic and biochemical effects of ligands and metal complexes of alpha-N-heterocyclic carboxaldehyde thiosemicarbazones.

Several alpha-N-heterocyclic carboxaldehyde thiosemicarbazones and their iron and copper complexes have been tested for their cytotoxicity and inhibiting activity against DNA synthesis under controlled metal conditions. No ligands show cytotoxicity against Ehrlich cells at the concentrations tested, while some iron and copper complexes are active. In contrast, the ligands inhibit DNA synthesis at much lower concentrations than used above. Similarly, the metal complexes are effective inhibitors at concentrations much below those necessary to demonstrate cytotoxicity. In addition, the iron complexes of 1-formylisoquinoline thiosemicarbazone, 2-formylpyridine thiosemicarbazone, and 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone were shown to be three- to sixfold more active than their free ligands as inhibitors of partially purified ribonucleotide reductase to which no iron has been added. The copper complex of 2-formylpyridine thiosemicarbazone was slightly more active than the free ligand against the reductase.

Animals↗
PubMed1991

[Differentiation activity of pyridoxal thiosemicarbazone and its copper and cobalt complexes on Friend erythroleukemia cells].

Thiosemicarbazones are a wide group of organic derivatives whose biological activities are a function of the parent aldehyde or ketone and of the coordination metal type. Some thiosemicarbazones possess a broad spectrum of potentially useful chemotherapeutic properties (antitumor, antibacterial, antiviral, antimalarial). The present study reports the biological effects of pyridoxal thiosemicarbazone, H2L, and relative complexes with copper, [(Cu(HL)(OH2))2]++ and with cobalt, [Co(III)(L)(HL)] on the differentiation of Friend erythroleukemia cells (FLC). They are murine proerythroblasts chronically infected by a producing Friend leukemia virus complex; their exposure to dimethylsulfoxide (Me2SO) or other chemical agents induces these cells to terminal erythroid differentiation, therefore these cells represent a good model of differentiation in vitro. Here we describe induction differentiation experiment of pyridoxal thiosemicarbazone and relative complexes of copper and cobalt on FLC performed with concentrations of 50 ug/ml (ligand), 2 ug/ml (complexes). These have little effects on cell proliferation at doses used in these experiments. Higher doses have evident cytotoxic effects. The treatment with the copper complex induces a moderate differentiation of FLC and enhances effects on erythroid differentiation of Me2SO-induced FLC. On the contrary H2L and [Co(III)(L)(HL)] haven't inducing effects or enhancing effects on Me2SO-induced FLC hemopoietic differentiation. In conclusion, the present study shows that copper complexes of pyridoxal thiosemicarbazone exert action of inducing agent and are able to enhance Me2SO-induced FLC hemopoietic differentiation.

Animals↗
PubMed1976

Synthesis of site-directed chelating agents II: 2-formyl-3-hydroxy-4,5-bis (hydroxymethyl)pyridine thiosemicarbazone.

2-Formyl-3-hydroxy-4,5-bis(hydroxymethyl)pyridine thiosemicarbazone was synthesized in an attempt to direct the chelating potential of this agent to the active site of the zinc-requiring enzyme pyridoxal phosphokinase. Evaluation of the antineoplastic activity of this agent in the sarcoma 180 and L-1210 leukemia systems in mice showed potent activity. The presence or absence of pyridoxine hydrochloride in the diet did not influence the degree of inhibition of the growth of sarcoma 180 ascites cells. In addition, 2-formyl-3-hydroxy-4,5-bis(hydroxymethyl)pyridine thiosemicarbazone was inactive against a subline of sarcoma 180 resistant to 1-formylisoquinoline thiosemicarbazone, suggesting that the former agent may have a biochemical mechanism of action similar to that of the latter. In keeping with this expectation, 2-formyl-3-hydroxy-4,5-bis(hydroxymethyl)pyridine thiosemicarbazone inhibited the synthesis of DNA but not of RNA or protein in sarcoma 180 ascites cells in vitro.

Animals↗
PubMed2004

Electrospray ionization mass spectrometry in the structural characterization of some diphenyllead(IV) thiosemicarbazonates.

The behavior in electrospray ionization mass spectrometry (ESI-MS) conditions of some complexes formed by Pb(C6H5)2(OAc)2 with salicylaldehyde, 2-ketobutyric acid, pyridine-2-carbaldehyde, 2-acetylpyridine, and 2-benzoylpyridine thiosemicarbazones, was studied in detail with the aid of collisional experiments performed by ion trap. The homoleptic complexes of tridentate thiosemicarbazonate dianions (TSC2-) lose the phenyl groups first, destabilizing the high oxidation state of the metal and leading to Pb(II) complexes in which the TSC2- ligand or a part of it remains coordinated to the metal. The main difference among the complexes derives from the presence of a carboxylate group on the 2-ketobutyric acid thiosemicarbazonato ligand, which probably interacts with a Na+ cation leading to ESI-generated [M+Na]+ species. In the absence of the carboxylate group, the production of abundant protonated molecules is observed. These different behaviors have been rationalized from the structural point of view. The heteroleptic mononuclear complexes, including thiosemicarbazonate and AcO- monoanions in the coordination sphere, do not yield intact ionized molecular species, and the most abundant ESI-generated ion is due to AcO- loss. The spectrum of the binuclear heteroleptic complex formed by the salicylaldehyde thiosemicarbazonate monoanion is conditioned by the weak bonding interaction displayed by the acetate bridge. MSn experiments yield important information on the relative ligand-Pb bond strengths. This work forms part of the search for chelating agents that can be used for effective chemotherapy of organolead poisoning.

Chelating Agents↗
PubMed1986

Selective inhibition of herpes simplex virus ribonucleoside diphosphate reductase by derivatives of 2-acetylpyridine thiosemicarbazone.

The effects of thiosemicarbazone derivatives of 2-acetylpyridine on mammalian and viral ribonucleoside diphosphate reductases were investigated. The enzymes were partially purified from uninfected and herpes simplex virus type-1 (HSV-1)-infected KB cells by sequential salt fractionation with streptomycin sulfate and ammonium sulfate and by affinity chromatography on ATP-agarose. The five thiosemicarbazone derivatives investigated were all potent inhibitors of the virus-induced reductase. Fifty percent inhibitory concentrations (IC50 values) range from 2 to 13 microM. Four of the five derivatives also were inhibitors of the host cell reductase (IC50 values = 7-34 microM). A semicarbazone was inactive against the cellular enzyme and relatively weak as an inhibitor of the viral enzyme (IC50 = 340 microM). Four of six compounds were preferential inhibitors of the viral reductase based on a comparison of IC50 values (5- to greater than 85-fold difference). Kinetic experiments revealed that inhibition of the HSV-1 reductase by the thiosemicarbazones was noncompetitive with respect to CDP and dithiothreitol. A comparison of the inhibitory effects of 2-acetylpyridine thiosemicarbazone itself on viral reductase and on virus replication in vitro demonstrated a similarity in the dose-response relationships for the two parameters. This observation supports the hypothesis that the HSV-induced ribonucleoside diphosphate reductase is an important target for the design of antiviral drugs.

Antiviral Agents↗
PubMed2005

Preparation of [61Cu]-2-acetylpyridine thiosemicarbazone complex as a possible PET tracer for malignancies.

Due to the interesting anti-proliferative properties of copper-thiosemicarbazone complexes, the production of a (61)Cu-labeled thiosemicarbazone, i.e. 2-acetylpyridine thiosemicarbazone (APTS) was investigated. Copper-61 (T(1/2)=3.33 h) was produced via the (64)Zn(p,alpha)(61)Cu nuclear reaction using a natural zinc target irradiated with 22 MeV protons for 500 microAh. The (61)Cu was separated from the irradiated target material by a two-step method and converted to acetate; this yielded a final activity of 222 GBq (6.0 Ci), with a radiochemical yield of >95%. The (61)Cu-acetate was mixed with 2-acetylpyridine thiosemicarbazone for 30 min at room temperature to yield [(61)Cu]APTS with a radiochemical yield of more than 80%. Colorimetric methods showed that residual chemical impurities in the product were below the accepted limits. Radio thin layer chromatography (RTLC) showed a radiochemical purity of more than 99% after C(18) column chromatography. A specific activity of about 370-740 MBq/mmol (10-20 Ci/mmol) was obtained. The stability of the final product was checked in the absence and presence of human serum at 37 degrees C for up to 3 h. The partition coefficient of the final complex was also determined.

Animals↗
PubMed2004

In vitro activity and mechanism of action against the protozoan parasite Trypanosoma cruzi of 5-nitrofuryl containing thiosemicarbazones.

The in vitro growth inhibition activity of new thiosemicarbazone derivatives against the protozoan parasite Trypanosoma cruzi, the causative agent of American trypanosomiasis, are described. The designed compounds combine in the same molecule the thiosemicarbazone function, recently described as a potent cruzain-inhibitor moiety, and the recognised 5-nitrofuryl group, an oxidative stress promoter. Some of the derivatives were found to be very active against the cultured (epimastigote) form of the parasite, being 1.5-1.7-fold more active than the reference compound, Nifurtimox. Free radicals production was detected when the compounds were incubated in presence of mammalian-liver microsomes. The thiosemicarbazones' capacity to act as pharmacophore in the cruzain inhibition process was theoretically analysed. Frontier molecular orbital HOMO was found as an adequate descriptor in this process. Acute in vivo toxicity of two of the more active derivatives was evaluated. The results showed that these compounds are among the most potent 5-nitrofuryl derivatives tested against this parasite thus support further in vivo studies of some of these thiosemicarbazones.

Animals↗
PubMed2000

EPR characterization of mono(thiosemicarbazones) copper(II) complexes. Note II.

Copper(II) complexes with thiosemicarbazones have been shown to be more active in cell destruction, in the inhibition of DNA synthesis than the uncomplexed ligand. Several derivatives of thiosemicarbazones and their iron and copper complexes have been studied for their cytotoxicity and inhibiting activity against DNA synthesis. In the present work complexes formed in H2O-DMSO solution between copper(II) and the acetophenone thiosemicarbazone (ATSC) and the o-aminobenzaldehyde thiosemicarbazone (o-NH2TSC) have been studied. EPR studies have been performed at different pH values and metal-to-ligand ratios. The spectra have been recorded at both room (298 K) and low temperatures (120 K). A possible relationship between structure and activity is attempted on the basis of the EPR data.

Antineoplastic Agents↗
PubMed2001

Synthesis, characterisation and antiamoebic activity of new thiophene-2-carboxaldehyde thiosemicarbazone derivatives and their cyclooctadiene Ru(II) complexes.

Reaction of new thiosemicarbazones (1-4) derived from thiophene-2-carboxaldehyde and cycloalkylaminothiocarbonylhydrazine with [Ru(eta(4)-C8H12)(CH3CN)2Cl2] leads to form complexes (1a-4a) of the type [Ru(eta(4)-C8H12)(TSC)Cl2] (where TSC=thiosemicarbazone). All the compounds have been characterised by elemental analysis, IR, 1H NMR, electronic spectra and thermogravimetric analysis. It is concluded that the thionic sulphur and the azomethine nitrogen atom of the ligands are bonded to the metal ion. In vitro antiamoebic screening against (HK-9) strain of Entamoeba histolytica indicated that the Ru(II) complexes of thiophene-2-carboxaldehyde thiosemicarbazones were found more active than the thiosemicarbazones.

Animals↗
PubMed2002

New 2-(1-adamantylcarbonyl)pyridine and 1-acetyladamantane thiosemicarbazones-thiocarbonohydrazones: cell growth inhibitory, antiviral and antimicrobial activity evaluation.

The new thiosemicarbazones and thiocarbonohydrazones derived from 2-(1-adamantylcarbonyl)pyridine and 1-acetyladamantane were synthesized and evaluated for their inhibitory effect on tumor cell proliferation and their antiviral and antimicrobial activity. Thiosemicarbazone inhibited tumor cell proliferation (GI50's range: 2.4-100 microM and mean GI50 43.9 microM against various human leukemic cell lines) while thiosemicarbazone and thiocarbonohydrazone 5d exhibited significant inhibition of tumor cell proliferation (GI50's range 2.3-23.6 microM and mean GI50 7.2 microM for and GI50's range 2.4-32.4 microM and mean GI50 12.8microM for ). These GI50 values are comparable to that of 2-acetylpyridine thiosemicarbazone an important lead in TSC's family. The compounds did not afford specific activity against any of the viruses tested when examined at non-toxic concentrations. A weak activity was found for thiocarbonohydrazones against Gram-(+) bacteria (MIC(50) 117.3 and 133 microM, respectively). Using a combination of molecular mechanics calculations and NOE spectroscopy it was shown that the parent compounds and have opposite configuration around C=N bond. Whether this difference in structure can be correlated with the biological activity will be investigated in future studies.

Bacteria↗
PubMed2003

New palladium(II) complexes of 5-nitrothiophene-2-carboxaldehyde thiosemicarbazones. synthesis, spectral studies and in vitro anti-amoebic activity.

Thiosemicarbazones (1-7) and their palladium(II) complexes (1a-7a) of the type [Pd(TSCN)Cl(2)] (where TSCN=thiosemicarbazone) were prepared from 5-nitro thiophene-2-carboxaldehyde and [Pd(DMSO)(2)Cl(2)], respectively. Coordination via the thionic sulphur and the azomethine nitrogen atom of the thiosemicarbazones to the metal ion were confirmed by spectral data. These compounds were screened in vitro against (HK-9) strain of Entamoeba histolytica possess amoebicidal properties. Enhancement of antiamoebic activity resulted due to the introduction of palladium metal in the thiosemicarbazone moiety. The most promising of the group tested are [Pd(5-N-2-TCA-COTSCN)Cl(2)] and [Pd(5-N-2-TCA-AdmTSCN)Cl(2)] comparable to that of metronidazole.

Amebicides↗
PubMed1976

Potential antitumor agents. 14. 4-Substituted 2-formylpyridine thiosemicarbazones.

A series of 4-substituted 2-formylpyridine thiosemicarbazones has been synthesized which contain a tertiary N at the 4 position. These materials were obtained by reacting 4-nitro-2-picoline N-oxide, either directly or after conversion to the corresponding 4-chloro derivative, with a variety of secondary amines. Rearrangement of the 4-substituted 2-picoline N-oxides with Ac2O yielded respective methyl acetates, which upon acid hydrolysis, MnO2 oxidation, and reaction with thiosemicarbazide resulted in the desired compounds. An alternate procedure which consisted of reacting 4-chloro-2-formylpyridine ethylene acetal with various amines, followed by hydrolysis and reaction with thiosemicarbazide, was also employed. Introduction of an alkyl group at the 3 position of the pyridine ring of 4-morpholino-2-formylpyridine thiosemicarbazone was achieved by utilizing 2,3-dimethyl-4-nitropyridine N-oxide; this material was converted to the corresponding 4-chloro derivative which was then subjected to nucleophilic substitution. 4-Morpholino-2-formylpyridine thiosemicarbazone was the most active antineoplastic agent of this series in mice bearing Sarcoma 180 ascites cells and was significantly superior to 5-hydroxy-2-formylpyridine thiosemicarbazone in this test system.

Animals↗
PubMed1996

Synthesis and biological activity of 3- and 5-amino derivatives of pyridine-2-carboxaldehyde thiosemicarbazone.

A series of 3- and 5-alkylamino derivatives, as well as other structurally modified analogues of pyridine-2-carboxaldehyde thiosemicarbazone, have been synthesized and evaluated as inhibitors of CDP reductase activity and for their cytotoxicity in vitro and antineoplastic activity in vivo against the L1210 leukemia. Alkylation of 3- and 5-amino-2-(1,3-dioxolan-2-yl)pyridines (1, 2) resulted in corresponding 3-methylamino, 5-methylamino, 3-allylamino, 5-ethylamino, 5-allylamino, 5-propylamino, and 5-butylamino derivatives (5, 6, and 11-15), which were then condensed with thiosemicarbazide to yield the respective thiosemicarbazones (7, 8, and 16-20). Oxidation of 3,5-dinitro-2-methylpyridine (21) with selenium dioxide, followed by treatment with ethylene glycol and p-toluenesulfonic acid, produced the cyclic ethylene acetal, 23. Oxidation of 2-(1,3-dioxolan-2-yl)-4-methyl-5-nitropyridine (26) with selenium dioxide, followed by sequential treatment with sodium borohydride, methanesulfonyl chloride, and morpholine afforded the morpholinomethyl derivative 30. Catalytic hydrogenation of 23 and 30 with Pd/C yielded the corresponding amino derivatives 24 and 31. Catalytic hydrogenation of 5-cyano-2-methylpyridine (33) with Raney nickel, followed by treatment with acetic anhydride, gave the amide derivative 35. N-Oxidation of 35, followed by rearrangement with acetic anhydride, produced the acetate derivative, 5-[(acetylamino)methyl]-2-(acetoxymethyl)pyridine (37). Repetition of the N-oxidation and rearrangement procedures with compound 37 yielded the diacetate derivative 39. Condensation of compounds 24, 31, and 39 with thiosemicarbazide afforded the respective 3,5-diaminopyridine-, 4-(4-morpholinylmethyl)-5-aminopyridine-, and 5-(aminomethyl)pyridine-2-carboxaldehyde thiosemicarbazones (25, 32, and 40). The most biologically active compounds synthesized were the 5-(methylamino)-, 5-(ethylamino)-, and 5-(allylamino)pyridine-2-carboxaldehyde thiosemicarbazones (8, 17, and 18), which were potent inhibitors of ribonucleotide reductase activity with corresponding IC50 values of 1.3, 1.0, and 1.4 microM and which produced significant prolongation of the survival time of L1210 leukemia-bearing mice, with corresponding optimum % T/C values of 223, 204, and 215 being obtained when administered twice daily for six consecutive days at dosages of 60, 80, and 80 mg/kg, respectively.

Animals↗
PubMed1973

Inhibition of RNA-dependent DNA polymerase of Rous sarcoma virus by thiosemicarbazones and several cations.

The RNA-dependent DNA polymerase of Rous sarcoma virus is inhibited by N-methyl isatin beta-thiosemicarbazone and by thiosemicarbazide, but not by semicarbazide. These inhibitors also inactivate, upon contact with the virion, the transforming ability of Rous sarcoma virus. Sulfhydryl donors, such as 2-mercapto-ethanol, can prevent these effects. The RNA-directed activity of the purified polymerase is inhibited to a greater degree than is the DNA-directed activity. Two cations, Cu(++) and Hg(++), can inhibit RNA-dependent DNA polymerase and inactivate the transforming ability of the virus. Synergism between N-methyl isatin beta-thiosemicarbazone and Cu(++) occurs, since treatment of the virus with a low dose of either N-methyl isatin beta-thiosemicarbazone or Cu(++) has little effect; however, when the two compounds are mixed together, significant inactivation occurs. This observation supports the hypothesis that the antiviral action of thiosemicarbazones is a function of their ability to act as a ligand for metallic ions. Several cations (Ag(+), Co(++), Zn(++), Cd(++), and Ni(++)) significantly inactivate the RNA-dependent DNA polymerase, but have little effect on the transforming ability. In view of this result, the conclusion that the enzyme activity is required for transformation remains open to question.

Animals↗
PubMed1986

Structure-activity relationships among alpha-(N)-heterocyclic acyl thiosemicarbazones and related compounds as inhibitors of herpes simplex virus type 1-specified ribonucleoside diphosphate reductase.

2-Acetylpyridine thiosemicarbazone, a potent antiviral drug, and 13 analogues were examined as inhibitors of partially purified herpes simplex virus type 1-specified ribonucleoside diphosphate reductase. N4,N4-Azacycloheptane derivatives were more active than their N4-unsubstituted analogues. Selenosemicarbazones were similar in potency to their thiosemicarbazone congeners, whereas a related semicarbazone was much less active. Maximum inhibition was observed when an ethylidene side-chain was present in the compounds. No discernible trend in potency was observed when the pyridine moiety was replaced by quinoline or isoquinoline. Thiosemicarbazide derivatives were less potent than their unsaturated thiosemicarbazone analogues. Inhibitory potencies increased at longer incubation times consistent with the hypothesis that thiosemicarbazones inactivate the enzyme in a time-dependent manner.

Ribonucleoside Diphosphate Reductase↗