Open Access

Synthesis of Mercapto Heterocyclic Derivatives of 1-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)-2-thio-propan-1-one and its Biological Activities

Venugopal , Department of Chemistry, National College, Tiruchirappalli, TN, India. Dhandayutham, drdsaro@gmail.com
Department of Chemistry, National College, Tiruchirappalli, TN, India. Manivachagam , Department of Botany, Annamalai University, Annamalainagar, TN, India. Gnanaprakasam Department of Botany, Annamalai University, Annamalainagar, TN, India.

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Abstract

In the present study, a new series of mercapto heterocyclic derivatives of 1-(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)-2-thio-propan-1-one derivatives are synthesized. The chemical structures were confirmed by IR, 1H-NMR and mass spectral analysis. The compounds were screened for antibacterial and antifungal activity. It shows good antibacterial and antifungal activity for most of synthesized compounds.

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 Askin, D., Eng, K.K., Rossen, K., Purick, R.M., Wells, K. M., Volante, R.P. and Reider, P.J., Highly diasteroselective reaction of a chiral, non-racemic amide enolate with (S)-glycidyl tosylate. Synthesis of the orally active HIV-1 protease inhibitor L-735,524, Tetrahedron Lett., 35, 673–676 (1994).

doi:10.1016/S0040-4039(00)75787-X

Bean, D. C. and Wareham, D. W., Paradoxical effect of 1-(1-naphthylmethyl)-piperazine on resistance to tetracyclines in multidrug-resistant Acinetobacter baumannii, J. Antimicrobl. Chemother., 63, 349-352 (2009).

doi: 10.1093/jac/dkn493

Becker, O. M., Dhanoa, D. S., Marantz, Y., Chen, D.,Shacham, S., Cheruku, S., Heifetz, A., Mohanty, P., Fichman, M., Shradendu, A., Nudelman, R., Kauffman, M. and Noiman, S., An Integrated in Silico 3D Model-Driven Discovery of a Novel, Potent, and Selective Amidosulfonamide 5-HT1A Agonist (PRX-00023) for the Treatment of Anxiety and Depression, J. Med. Chem., 49, 3116-3135 (2006).

doi: 10.1021/jm0508641

Berkheij M., van der Sluis L., Sewing C.J., den Boer D., Terpstra J.W., Hiemstra H., Bakker W.I.I., van den Hoogenband A. and  van Haarseveen J.H., Synthesis of 2-substituted piperazines via direct α-lithiation, Tetrahedron Lett., 46,2369–2371 (2005).

doi:10.1016/j.tetlet.2005.02.085

Chaudhary, P., Kumar, R., Verma, A. K., Singh,  D.,Yadav, V., Chhillar, A. K., Sharmab, G. L. and Chandraa, R., Synthesis and antimicrobial activity of N-alkyl and N-aryl piperazine derivatives, Bioorg. Med. Chem., 14, 1819-1826 (2006).

doi:10.1016/j.bmc.2005.10.032

Chen, J. J., Lu, M., Jing, Y. K. and Dong, J. H., The synthesis of l-carvone and limonene derivatives with increased antiproliferative effect and activation of ERK pathway in prostate cancer cells, Bioorg. Med. Chem., 14, 6539-6547 (2006).

doi:10.1016/j.bmc.2006.06.013

Coban, A. Y., Bayram, Z., Sezgin, F. M. and Durupinar, B., Effect of efflux pump inhibitor 1-(1-naphthylmethyl)-piperazine to MIC values of ciprofloxacin in ciprofloxacin resistant gram-negative bacteria, Mikrobiyoloji Bulteni., 43, 457-461 (2009).

Cunico, W., Gomes, C. R. B., Moreth, M., Manhanini, D. P., Figueiredo, I. H., Penido, C., Henriques, M. G. M. O., Varotti, F. P. and Krettli, A. U., Synthesis and antimalarial activity of hydroxyethylpiperazine derivatives, Eur. J. Med. Chem., 44, 1363-1368 (2009).

doi:10.1016/j.ejmech.2008.04.009

Dorsey, B.D., Levin, R.B., McDaniel, S.L., Vacca, J.P., Guare, J.P., Darke, P.L., Zugay, J.A., Emini, E.A. and Schleif, W.A., The design of a potent and orally bioavailable HIV protease inhibitor. J. Med. Chem., 37, 3443–3451 (1994).

doi: 10.1021/jm00047a001

Farzaliev, V. M., Abbasova, M. T., Ashurova, A. A., Babaeva, G. B., Ladokhina, N. P. and  Kerimova, Y. M., Synthesis of N,N′-bis(alkyloxymethyl)piperazines and examination of their antimicrobial properties, Russian J. Appl. Chem., 82, 928-930 (2009).

doi: 10.1134/S107042720905036X

Foroumadi, A., Ghodsi, S., Emami, S., Najjari, S., Samadi, N., Faramarzi, M. A., Beikmohammadi, L., Shirazi, F. H. and Shafiee, A., Synthesis and antibacterial activity of new fluoroquinolones containing a substituted N-(phenethyl)piperazine moiety, Bioorg. Med. Chem. Lett., 16, 3499-3503 (2006).

doi: 10.1016/j.bmcl.2006.03.103

Foroumadi, A., Emami, S., Mansouri, S., Javidnia, A., Saeid-Adeli, N., Shirazi, F. H. and Shafiee, A., Synthesis and antibacterial activity of levofloxacin derivatives with certain bulky residues on piperazine ring, Eur. J. Med. Chem., 42, 985-992 (2007).

doi:10.1016/j.ejmech.2006.12.034

Gabriel, F.E., Gu, J., Slater, L.M., Hara, K. and Jacobs, J. W., Tumor apoptosis induced by epoxide-containing piperazines, a new class of anti-cancer agents. Cancer Chemother. Pharmacol., 45, 183–191 (2000).

doi: 10.1007/s002800050028

Gillet, R., Jeannesson, P., Sefraoui, H., Arnould-GueArin, M., Kirkiacharian, L.S., Jardillier, J.C. and Pieri, F., Piperazine derivatives of butyric acid as differentiating agents in human leukemic cells. Cancer Chemother. Pharmaco., 41, 252–255 (1998).

doi: 10.1007/s002800050737

Guo C.C., Tong R.B. and Li, K.L., Chloroalkyl piperazine and nitrogen mustard porphyrins: Synthesis and anticancer activity,  Bioorg. Med. Chem., 12, 2469–2475 (2004).

doi:10.1016/j.bmc.2004.01.045

Hulme, C., Ma, L., Romano, J. and Morisette, M., Novel applications of ethyl glyoxalate with the Ugi MCR. Tetrahedron Lett., 40, 5295–5299 (1999).

doi:10.1016/S0040-4039(99)00960-0

Kuldeep Singh, Siddiqui, H.H., Pragati Shakya, Paramdeep bagga, Arun Kumar, Khalid, M., Arif, M., and Shashi Alok. Piperazine – A Biologically active scaffold. IJPSR, 6, 10, 4145-58 (2015).

doi: 10.13040/IJPSR.0975-8232.6(10).4145-58

Lohray, B. B., Lohray, V. B., Srivastava, B. K., Gupta, S., Solanki, M., Pandya, P. and Kapadnis, P., Novel 4-N-substituted aryl pent-2-ene-1,4-dione derivatives of piperazinyloxazolidinones as antibacterials,  Bioorg. Med. Chem. Lett., 16, 1557-1561 (2006).

doi:10.1016/j.bmcl.2005.12.025

Mayence, A., Eynde, J. J. V., LeCour, L., Jr Walker, L. A., Tekwani, B. L. and Huang, T. L., Piperazine-linked bisbenzamidines: a novel class of antileishmanial agents,  Eur. J. Med. Chem., 39, 547-553 (2004).

doi:10.1016/j.ejmech.2004.01.009

Nee Kosoczky Bolya Balla, Nee Petocz Lujza Erdelyi, Eniko Kiszelly, Jeno Korosi, Nee Konya Lay and Nee Czibula Gabriella Szabo, EGYT. Pyridine Derivatives Having Antidepressant Activity. U.S. Patent 3,865,828, 11 February (1975).

Penjišević, J., Šukalović, V., Andrić, D., Kostić-Rajačić, S., Šoškić, V. and Roglić, G., 1‐Cinnamyl‐4‐(2‐methoxyphenyl)piperazines: Synthesis, Binding Properties, and Docking to Dopamine (D2) and Serotonin (5‐HT1A) Receptors, Arch. Pharm. Chem. Life Sci., 340, 456-465 (2007).

doi: 10.1002/ardp.200700062

Phillips O. A., Udo E. E. and Samuel S. M., Synthesis and structure–antibacterial activity of triazolyl oxazolidinones containing long chain acyl moietyEur. J. Med. Chem., 43, 1095-1104 (2008).

doi:10.1016/j.ejmech.2007.07.006

Rokosz, L. L., Huang, C. Y., Reader, J. C., Stauffer, T. M., Chelsky, D., Sigal, N. H., Ganguly, A. K. and Baldwin, J. J., Surfing the piperazine core of tricyclic farnesyltransferase inhibitors, Bioorg. Med.Chem. Lett., 15, 5537-5543 (2005).

doi: 10.1016/j.bmcl.2005.08.074

Rosen, K., Weissman, S. A., Sager, J., Reamer, R. A., Askin, D., Volante, R.P. and Reider, P.J., Asymmetric Hydrogenation of tetrahydropyrazines: Synthesis of (S)-piperazine 2-tert-butylcarboxamide, an intermediate in the preparation of the HIV protease inhibitor indinavir. Tetrahedron Lett., 36, 6419–6422 (1995).

doi:10.1016/0040-4039(95)01345-I

Shami, P. J., Saavedra, J. E., Bonifant, C. L., Chu, J. X., Udupi, V., Malaviya, S., Carr, B. I., Kar, S., Wang, M. F., Jia, L., Ji, X. H. and Keefer, L. K., Antitumor Activity of JS-K [O2-(2,4-Dinitrophenyl) 1-[(4-Ethoxycarbonyl) piperazin-1-yl]diazen-1-ium-1,2-diolate] and Related O2-Aryl Diazeniumdiolates in Vitro and in Vivo, J. Med. Chem., 49, 14, 4356-4366 (2006).

doi: 10.1021/jm060022h

Smits, R. A., Lim, H. D., Hanzer, A., Zuiderveld, O. P., Guaita, E., Adami, M., Coruzzi, G., Leurs, R. and  Esch, I. J. P., Fragment Based Design of New H4 Receptor−Ligands with Anti-inflammatory Properties in Vivo, J. Med. Chem., 51, 2457-2467 (2008).

doi: 10.1021/jm7014217

Upadhayaya, R. S., Sinha, N., Jain, S., Kishore, N., Chandra, R. and Arora, S. K., Optically active antifungal azoles: synthesis and antifungal activity of (2R,3S)-2-(2,4-difluorophenyl)-3-(5-{2-[4-aryl-piperazin-1-yl]-ethyl}-tetrazol-2-yl/1-yl)-1-[1,2,4]-triazol-1-yl-butan-2-ol, Bioorg. Med. Chem.,12, 2225-2238 (2004).

doi: 10.1016/j.bmc.2004.02.014

Watkins, W. J., Chong, L., Cho, A., Hilgenkamp, R., Ludwikow, M., Garizi, N., Iqbal, N., Barnard, J., Singh, R., Madsen, D., Lolans, K., Lomovskaya, O., Oza, U., Kumaraswamy, P., Blecken, A., Bai, S., Loury, D. J., Griffitha, D. C. and Dudley, M. N.,  Quinazolinone fungal efflux pump inhibitors. Part 3: (N-methyl)piperazine variants and pharmacokinetic optimization, Bioorg. Med. Chem. Lett., 17, 2802-2806 (2007).

doi: 10.1016/j.bmcl.2007.02.047