SYNTHESIS, ANTICANCER AND ANTITUBERCULOSIS STUDIES FOR [1-(4-CHLOROPHENYL) CYCLOPROPYL] (PIPERAZINE-YL) METHANONE DERIVATES
Keywords:Piperazine, Aldehydes, Cyclopropane, Antituberculosis, Anticancer
Objective: Synthesis, anticancer and antituberculosis studies for 1-(4-Chlorophenyl) cyclopropyl] (piperazin-1-yl) methanone derivates 3a-j
Methods: A series of new [1-(4-Chlorophenyl) cyclopropyl] (piperazin-1-yl) methanone derivates were synthesized using reductive amination method in presence of sodium triacetoxyborohydride to yield piperzine derivatives 3a-j. The structures of all newly synthesized compounds have been characterised by elemental analysis and spectral studies.
Results: Five selected compounds have been screened for invitro anticancer activity against human breast cancer cell line MDA-MB-435 at 10, 20, 40 and 80 ÂµG/mL concentration using sulforhodamine B assay method. and Two compounds 3a and 3c have shown in vitro anticancer activity.
Five selected compounds have been screened for anti-tuberculosis activity using Middlebrook 7H-9 broth and standard strain of M. tb h37Rv. Three compounds 3a, 3b and 3c have shown significant antituberculosis
Conclusion: Synthesis of [1-(4-Chlorophenyl) cyclopropyl] (piperazin-1-yl) methanone derivates 3a-j simple and convenient method. Some of the tested compounds have exhibited significant antituberculosis and anticancer activity. Compound 3c showed both antituberculosis and anticancer activity.
Shchekotikhim AE, Shtil AA, Luzikov YN, Bobrysheva TV, Buyanov VN, Preobrazhenskaya MN. 3-Aminomethyl derivatives of 11-dihydroxynaphtho[2,3-f]indole-5,10-dione for circumvention of anticancer drug resistance Bioorg. J Med Chem 2005;4:2285-91.
Hou X., Ge, T. Wang Z., Guo, J. Cui W., Cheng, C. Lai T., Li R., Dithiocarbamic acid esters as anticancer agent. Part 1:4-Substituted-piperazine-1-carbodithioic acid 3-cyano-3,3-diphenyl-propyl esters Bioorg. J Med Chem Letters 2006;16:4214-19.
A. Kumar C. S., Swamy S. N, Thimmegowda N. R., Prasad S. B. B., Yip G.W., Rangappa K. S., Synthesis and evaluation of 1-benzhydryl-sulfonyl-piperazine derivatives as inhibitors of MDA-MB-231 human breast cancer cell proliferation. J Med Chem Res 2007;16:179-87.
Kamal A, Rajender D, Reddy DR, Reddy MK, Balakishan G, Shaik TB, et al. Remarkable enhancement in the DNA-binding ability of C2-fluoro substituted pyrrolo[1-c][1,4]benzodiazepines and their anticancer potential. J Bioorg Med Chem 2009;2(17):1557-72.
Kamal A, Vijaya Bharathi E, Janaki Ramaiah M, Surendranadha Reddy J, Dastagiri D, Viswanath A, et al. Synthesis, anticancer activity and apoptosis inducing ability of anthranilamide-PBD conjugates. J Bioorg Med Chem Lett 2010;20(11):3310-3.
Chetan B, Bunha M, Jagrat M, Sinha BN, Saiko P, Graser G, et al. Design, synthesis and anticancer activity of piperazine hydroxamates and their histone deacetylase (HDAC) inhibitory activity. J Bioorg Med Chem Lett 2010;20(13):3906-10.
Foroumadi A, Emami S, Mansouri S, Javidnia A, Saeid-Adeli N, Shirazi FH, et al. Synthesis and antibacterial activity of levofloxacin derivatives with certain bulky residues on piperazine ring. Eur J Med Chem 2007;42(7):985-92.
Cai M, Li Z, Fan F, Huang Q, Shao X, Song G, et al. Design and Synthesis of Novel Insecticides Based on the Serotonergic Ligand 1-[(4-Aminophenyl) ethyl]-4-[3-(trifluoromethyl) phenyl] piperazine (PAPP). J Food Chem 2008;58(5):58-62.
(a) K. K Singh, C. S. Joshi, C. S. Mathela, Synthesis and in vitro antibacterial activityof N-alkyl and N-aryl piperazine derivatives. Ind J Chem 50(2)B, 2011, 196-200.
(b) A. Shafiee, Z. M. Haddad, N. Mohammadosseini, J. Khalafy, S. Emami, M.H Moshafi, M. Sorkhi, A. Foroumadi, Mannich bases of 7-piperazinylquinolones and kojic acid derivatives: Synthesis, in vitro antibacterial activity and in silicostudy. Daru J Pharm Sci 2008;16(3):189-95.
Bali A, Sharma K, Bhalla A, Bala S, Reddy D, Singh A, et al. Synthesis, evaluation and computational studies on a series of acetophenone based 1-(aryloxypropyl)-4-(chloroaryl) piperazines as potential atypical antipsychotics. Eur J Med Chem 2010;45(6):2656-62.
Todorovic A, Haskell-Luevano C. A review of melanocortin receptor small molecule ligands. J Peptides 2005;26(10):2026-36.
Kundu B. Solid-phase strategies for the design and synthesis of heterocyclic molecules of medicinal interest. J Current Opinion in Drug Discovery and Development 2003;6(6):815-26.
Raval JP, Desai KR. synthesis and antimicrobial activity of new triazolo pyridinyl phenothiazines. J ARKIVOC 2005;13:21-8.