Methyl-2-arylidene hydrazinecarbodithioates: synthesis and biological activity
-
Manojkumar Mahapatra
,
Umasankar Kulandaivelu
Abstract
Methyl-2-arylidene hydrazine-carbodithioate has not been of particular interest to researchers even though its metal complexes are extensively reported on due to their biological activity. This study examined the cytostatic and antiviral activity of twelve methyl-2-arylidene hydrazinecarbodithioates reported by many researchers as intermediates for the synthesis of thiosemicarbazides and the preparation of their metal complexes. Compounds IIc, IIi, and IIl with tridentate ligand features were found to have the lowest IC50 value (6.5 μM, ≈ 1 μM, and 0.8 μM, respectively) against HL60 human promyelocytic leukemia cells. They were also most inhibitory to human embryonic lung (HEL) fibroblast proliferation (5.3 μM, 17 μM, and 2.6 μM). Compound IIc and IIl show antiviral activity against wild-type herpes simplex virus (HSV), varicella zoster virus (VZV), and acyclovirresistant HSV; however, these activities were observed at concentrations at which the compounds also markedly inhibit HL60 and HEL cell proliferation.
[1] Audrieth, L. F., Scott, E. S., & Kippur, P. S. (1954). Hydrazine derivatives of the carbonic and thiocarbonic acids. I. The preparation and properties of thiocarbohydrazide. The Journal of Organic Chemistry, 19, 733–741. DOI: 10.1021/jo01370a006. http://dx.doi.org/10.1021/jo01370a00610.1021/jo01370a006Suche in Google Scholar
[2] Ali, M. A., Mirza, A. H., Nazimuddin, M., Dhar, P. K., & Butcher, R. J. (2002). Preparation, characterization and antifungal properties of nickel(II) complexes of tridentate ONS ligands derived from N-methyl-S-methyldithiocarbazate and the X-ray crystal structure of the [Ni(ONMeS)CN]·H2O complex. Transition Metal Chemistry, 27, 27–33. DOI: 10.1023/a:1013434113299. http://dx.doi.org/10.1023/A:101343411329910.1023/A:1013434113299Suche in Google Scholar
[3] Beraldo, H., & Gambinob, D. (2004). The wide pharmacological versatility of semicarbazones, thiosemicarbazones, and their metal complexes. Mini-Reviews in Medicinal Chemistry, 4, 31–39. DOI: 10.2174/1389557043487484. http://dx.doi.org/10.2174/138955704348748410.2174/1389557043487484Suche in Google Scholar
[4] Cao, S. L., Feng, Y. P., Jiang, Y. Y., Liu, S. Y., Ding, G. Y., & Li, R. T. (2005). Synthesis and in vitro antitumor activity of 4(3H)-quinazolinone derivatives with dithiocarbamate side chains. Bioorganic & Medicinal Chemistry Letters, 15, 1915–1917. DOI:10.1016/j.bmcl.2005.01.083. http://dx.doi.org/10.1016/j.bmcl.2005.01.08310.1016/j.bmcl.2005.01.083Suche in Google Scholar
[5] Casero, R. A., Klayman, D. L., Childs, G. E., Scovill, J. P., & Desjardins, R. E. (1980). Activity of 2-acetylpyridine thiosemicarbazones against Trypanosoma rhodesiense in vitro. Antimicrobial Agents and Chemotherapy, 18, 317–322. DOI: 10.1128/aac.18.2.317. http://dx.doi.org/10.1128/AAC.18.2.31710.1128/AAC.18.2.317Suche in Google Scholar
[6] Collins, F. M., Klayman, D. L., & Morrison, N. E. (1982). Activity of 2-acetylpyridine and 2-acetylquinoline thiosemicarbazones tested in vitro in combination with other antituberculous drugs. The American Review of Respiratory Disease, 125, 58–60. Suche in Google Scholar
[7] Das, A., Trousdale, M. D., Ren, S. J., & Lien, E. J. (1999). Inhibition of herpes simplex virus type 1 and adenovirus type 5 by heterocyclic Schiff bases of aminohydroxyguanidine tosylate. Antiviral Research, 44, 201–208. DOI: 10.1016/s0166-3542(99)00070-4. http://dx.doi.org/10.1016/S0166-3542(99)00070-410.1016/S0166-3542(99)00070-4Suche in Google Scholar
[8] Ettari, R., Bova, F., Zappal`a, M., Grasso, S., & Micale, N. (2010). Falcipain-2 inhibitors. Medicinal Research Reviews, 30, 136–167. DOI:10.1002/med.20163. 10.1002/med.20163Suche in Google Scholar PubMed
[9] Huang, W., Ding, Y., Miao, Y., Liu, M. Z., Li, Y., & Yang, G. F. (2009). Synthesis and antitumor activity of novel dithiocarbamate substituted chromones. European Journal of Medicinal Chemistry, 44, 3687–3696. DOI:10.1016/j.ejmech.2009.04.004. http://dx.doi.org/10.1016/j.ejmech.2009.04.00410.1016/j.ejmech.2009.04.004Suche in Google Scholar PubMed
[10] Jiang, Z. G., Lebowitz, M. S., & Ghanbari, H. A. (2006). Neuroprotective activity of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (PAN-811), a cancer therapeutic agent. CNS Drug Reviews, 12, 77–90. DOI: 10.1111/j.1527-3458.2006.00077.x. http://dx.doi.org/10.1111/j.1527-3458.2006.00077.x10.1111/j.1527-3458.2006.00077.xSuche in Google Scholar PubMed PubMed Central
[11] Kanwar, S. S., Lumba, K., Gupta, S. K., Katoch, V. M., Singh, P., Mishra, A. K., & Kalia, S. B. (2008). Synthesis and mycobactericidal properties of metal complexes of isonicotinoyldithiocarbazic acid. Biotechnology Letters, 30, 677–680. DOI: 10.1007/s10529-007-9601-5. http://dx.doi.org/10.1007/s10529-007-9601-510.1007/s10529-007-9601-5Suche in Google Scholar PubMed
[12] Katz, E. (1987). Thiosemicarbazones: inhibition of the growth of pox viruses and requirement for the growth of an isatin-β-thiosemicarbazone dependent mutant. Journal of Basic and Clinical Physiology and Pharmacology, 6, 119–130. DOI:10.1515/jbcpp.1987.6.2.119. http://dx.doi.org/10.1515/JBCPP.1987.6.2.11910.1515/JBCPP.1987.6.2.119Suche in Google Scholar
[13] Klayman, D. L., Bartosevich, J. F., Scott Griffin, T., Mason, C. J., & Scovill, J. P. (1979). 2-Acetylpyridine thiosemicarbazones. 1. A new class of potential antimalarial agents. Journal of Medicinal Chemistry, 22, 855–862. DOI: 10.1021/jm00193a020. http://dx.doi.org/10.1021/jm00193a02010.1021/jm00193a020Suche in Google Scholar
[14] Klayman, D. L., Lin, A. J., McCall, J. W., Wang, S. Y., Townson, S., Grögl, M., & Kinnamon, K. E. (1991). 2-Acetylpyridine thiosemicarbazones. 13. Derivatives with antifilarial activity. Journal of Medicinal Chemistry, 34, 1422–1425. DOI: 10.1021/jm00108a027. http://dx.doi.org/10.1021/jm00108a02710.1021/jm00108a027Suche in Google Scholar
[15] Kowol, C. R., Trondl, R., Heffeter, P., Arion, V. B., Jakupec, M. A., Roller, A., Galanski, M., Berger, W., & Keppler, B. K. (2009). Impact of metal coordination on cytotoxicity of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (triapine) and novel insights into terminal dimethylation. Journal of Medicinal Chemistry, 52, 5032–5043. DOI: 10.1021/jm900528d. http://dx.doi.org/10.1021/jm900528d10.1021/jm900528dSuche in Google Scholar
[16] Kumar, L., Sarswat, A., Lal, N., Sharma, V. L., Jain, A., Kumar, R., & Verma, V., Maikhuri, J. P., Kumar, A., Shukla, P. K., & Gupta, G. (2010). Imidazole derivatives as possible microbicides with dual protection. European Journal of Medicinal Chemistry, 45, 817–824. DOI:10.1016/j.ejmech.2009.10.021. http://dx.doi.org/10.1016/j.ejmech.2009.10.02110.1016/j.ejmech.2009.10.021Suche in Google Scholar
[17] Liberta, A. E., & West, D. X. (1992). Antifungal and antitumor activity of heterocyclic thiosemicarbazones and their metal complexes: current status. Biometals, 5, 121–126. DOI: 10.1007/bf01062223. http://dx.doi.org/10.1007/BF0106222310.1007/BF01062223Suche in Google Scholar
[18] Matesanz, A. I., & Souza, P. (2009). α-N-heterocyclic thiosemicarbazone derivatives as potential antitumor agents: a structure-activity relationships approach. Mini-Reviews in Medicinal Chemistry, 9, 1389–1396. DOI: 10.2174/138955709789957422. http://dx.doi.org/10.2174/13895570978995742210.2174/138955709789957422Suche in Google Scholar
[19] Neelam, B., Mannar, M., Fehmida, N., Alok, B., Sudha, B., & Amir, A. (2000). Palladium(II) complexes of NS donor ligandsderived from S-methyl-dithiocarbazate, S-benzyldithiocarbazate and thiosemicarbazide as antiamoebic agents. European Journal of Medicinal Chemistry, 35, 481–486. DOI: 10.1016/s0223-5234(00)00145-8. http://dx.doi.org/10.1016/S0223-5234(00)00145-810.1016/S0223-5234(00)00145-8Suche in Google Scholar
[20] Pandeya, S. N., & Dimmock, J. R. (1993). Recent evaluations of thiosemicarbazones and semicarbazones and related compounds for antineoplastic and anticonvulsant activities. Pharmazie, 48, 659–666. Suche in Google Scholar
[21] Ren, S., Wang, R., Komatsu, K., Bonaz-Krause, P., Zyrianov, Y., McKenna, C. E., Csipke, C., Tokes, Z. A., & Lien, E. J. (2002). Synthesis, biological evaluation, and quantitative structure-activity relationship analysis of new Schiff bases of hydroxysemicarbazide as potential antitumor agents. Journal of Medicinal Chemistry, 45, 410–419. DOI: 10.1021/jm010252q. http://dx.doi.org/10.1021/jm010252q10.1021/jm010252qSuche in Google Scholar PubMed
[22] Richardson, D. R., & Milnes, K. (1997). The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents II: the mechanism of action of ligands derived from salicylaldehyde benzoyl hydrazone and 2-hydroxy-1-naphthylaldehyde benzoyl hydrazone. Blood, 89, 3025–3038. 10.1182/blood.V89.8.3025Suche in Google Scholar
[23] Saxena, A., & Tandon, J. P. (1983). Antitumor activity of some diorganotin and tin(IV) complexes of Schiff bases. Cancer Letters, 19, 73–76. DOI: 10.1016/0304-3835(83)90138-6. http://dx.doi.org/10.1016/0304-3835(83)90138-610.1016/0304-3835(83)90138-6Suche in Google Scholar
[24] Scovill, J. P., Klayman, D. L., & Franchino, C. F. (1982). 2-Acetylpyridine thiosemicarbazones. 4. Complexes with transition metals as antimalarial and antileukemic agents. Journal of Medicinal Chemistry, 25, 1261–1264. DOI: 10.1021/jm00352a036. http://dx.doi.org/10.1021/jm00352a03610.1021/jm00352a036Suche in Google Scholar
[25] Shipman, C., Smith, S. H., Drach, J. C., & Klayman, D. L. (1981). Antiviral activity of 2-acetylpyridine thiosemicarbazones against herpes simplex virus. Antimicrobial Agents and Chemotherapy, 19, 682–685. DOI: 10.1128/aac.19.4.682. http://dx.doi.org/10.1128/AAC.19.4.68210.1128/AAC.19.4.682Suche in Google Scholar
[26] Singh, N. K., Singh, N., Prasad, G. C., Sodhi, A., & Shrivastava, A. (1997). Antitumor activity studies of newly synthesized N-salicyloyl-N′-(p-hydroxybenzthioyl)hydrazine and its copper(II) complex both in vivo and in vitro. Bioorganic & Medicinal Chemistry, 5, 245–251. DOI: 10.1016/s0968-0896(96)00243-x. http://dx.doi.org/10.1016/S0968-0896(96)00243-X10.1016/S0968-0896(96)00243-XSuche in Google Scholar
[27] T’ang, A., Lien, E. J., & Lai, M. M. C. (1985). Optimization of the Schiff bases of N-hydroxy-N′-aminoguanidine as anticancer and antiviral agents. Journal of Medicinal Chemistry, 28, 1103–1106. DOI: 10.1021/jm00146a022. http://dx.doi.org/10.1021/jm00146a02210.1021/jm00146a022Suche in Google Scholar PubMed
[28] Wnuk, S. F., & Robins, M. J. (2006). Ribonucleotide reductase inhibitors as anti-herpes agents. Antiviral Research, 71, 122–126. DOI:10.1016/j.antiviral.2006.03.002. http://dx.doi.org/10.1016/j.antiviral.2006.03.00210.1016/j.antiviral.2006.03.002Suche in Google Scholar PubMed
[29] Yu, Y., Kalinowski, D. S., Kovacevic, Z., Siafakas, A. R., Jansson, P. J., Stefani, C., Lovejoy, D. B., Sharpe, P. C., Bernhardt, P. V., & Richardson, D. R. (2009). Thiosemicarbazones from the old to new: iron chelators that are more than just ribonucleotide reductase inhibitors. Journal of Medicinal Chemistry, 52, 5271–5294. DOI: 10.1021/jm900552r. http://dx.doi.org/10.1021/jm900552r10.1021/jm900552rSuche in Google Scholar PubMed
© 2013 Institute of Chemistry, Slovak Academy of Sciences
Artikel in diesem Heft
- Enzymatic synthesis of kojic acid esters and their potential industrial applications
- KI-catalysed synthesis of 4-methylcatechol dimethylacetate and fragrant compound Calone 1951®
- Sequestration of supercritical CO2 by mercury oxide
- Assessment of the fate of some household micropollutants in urban wastewater treatment plant
- Synthesis in water-free DMF, characterization, electrical, and gas sensing properties of bis[2-(2-aminoethylamino)ethanol]copper(II) dibromide
- Mechanism of α-acetyl-γ-butyrolactone synthesis
- Spirocyclisation of phytoalexin 1-methoxybrassinin in the presence of Grignard reagents
- Synthesis of new aryl(hetaryl)-substituted tandospirone analogues with potential anxiolytic activity via reductive Heck type hydroarylations
- Methyl-2-arylidene hydrazinecarbodithioates: synthesis and biological activity
- Degradation products of proguanil — 4-chloroaniline and related components with regard to genotoxicity
- In situ bioconversion of compactin to pravastatin by Actinomadura species in fermentation broth of Penicillium citrinum
- Mineral element content in prized matsutake mushroom (Tricholoma matsutake) collected in China
Artikel in diesem Heft
- Enzymatic synthesis of kojic acid esters and their potential industrial applications
- KI-catalysed synthesis of 4-methylcatechol dimethylacetate and fragrant compound Calone 1951®
- Sequestration of supercritical CO2 by mercury oxide
- Assessment of the fate of some household micropollutants in urban wastewater treatment plant
- Synthesis in water-free DMF, characterization, electrical, and gas sensing properties of bis[2-(2-aminoethylamino)ethanol]copper(II) dibromide
- Mechanism of α-acetyl-γ-butyrolactone synthesis
- Spirocyclisation of phytoalexin 1-methoxybrassinin in the presence of Grignard reagents
- Synthesis of new aryl(hetaryl)-substituted tandospirone analogues with potential anxiolytic activity via reductive Heck type hydroarylations
- Methyl-2-arylidene hydrazinecarbodithioates: synthesis and biological activity
- Degradation products of proguanil — 4-chloroaniline and related components with regard to genotoxicity
- In situ bioconversion of compactin to pravastatin by Actinomadura species in fermentation broth of Penicillium citrinum
- Mineral element content in prized matsutake mushroom (Tricholoma matsutake) collected in China
