Ariliden Karbazol Hidrazitler: Sentezi ve Karakterizasyonu

Geniş farmakolojik etkinlikleri ve kendine özgü yapısal özellikleri nedeniyle, hidrazonlar ve karbazol alkaloitleri tıbbi kimyada büyük ilgi görmektedir. Bu çalışmada, karbazol hidrazit bileşiği ile benzaldehit türevleri arasındaki kondenzasyon reaksiyonu ile yüksek biyolojik aktiflik potansiyeline sahip olabilecek yeni karbazol açil hidrazon türevleri (3a-k) sentezlenmiştir. Sentezlenen türevlerin erime noktaları belirlendikten sonra, yapıları FT-IR ve 1H-NMR spektroskopik yöntemleri ile aydınlatılmıştır.

Arylidene Carbazole Carbohydrazides: Synthesis and Characterization

Because of the wide range of pharmacological activities and their distinctive structural features hydrazones and carbazole alkaloids have attracted considerable attention in medicinal chemistry. In this study, new carbazole acyl hydrozones (3a-k) which may have high biological activity potential, were synthesized with condensation reaction between carbazole hydrazide and benzaldehyde derivatives. After determination of the melting points of all synthesized derivatives, their structures were identified by FT-IR and 1 H-NMR spectroscopic methods.

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B. Koçyiğit Kaymakçıoğlu, E.E. Oruç Emre, S. Unsalan, S. Rollas, Antituberculosis activity of hydrazones derived from 4-fluorobenzoic acid hydrazide, Med. Chem. Res., 18 (2009) 277-286.
V. Judge, B. Nrasimhan, M. Ahuja, D. Sriram, P. Yogeeswari, E.D. Clercq, C. Pannecouque, J. Balzarini, Isonicotinic acid hydrazide derivatives: Synthesis, antimicrobial activity, and QSAR studies, Med. Chem. Res., 21 (2011) 1-20.
K.A. Metwally, L.M. Abdel-Aziz, E.M. Lashine, M.I. Husseiny, R.H. Badawy, Hydrazones of 2-arylquinoline-4-carboxylic acid hydrazides: synthesis and preliminary evaluation as antimicrobial agents, Bioorg. Med. Chem., 14 (2006) 8675-8682.
B.S. Holla, M. Mahalinga, M.S. Karthikeyan, B. Poojary, P.M. Akberali, N.S. Kumari, Synthesis, characterization and antimicrobial activity of some substituted 1,2,3-triazoles, Eur. J. Med. Chem., 40 (2005) 1173-1178.
D. Sarıgöl, D. Yüksel, G. Okay, A. Uzgören-Baran, Synthesis and structural studies of acyl hydrazone derivatives having tetrahydrocarbazole moiety, J. Mol. Struct., 1086 (2015) 146–152.
V.V. Syakaev, S.N. Podyachev, B.I. Buzykin, S. K. Latypov, W.D. Habicher, A.I. Konovalov, NMR study of conformation and isomerization of aryl- and heteroarylaldehyde 4-tertbutylphenoxyacetylhydrazones, J. Mol. Struct. 788 (2006) 55-62.
O. Unsal Tan, K. Ozden, A. Rauk, A. Balkan, Synthesis and cyclooxygenase inhibitory activities of some N-acylhydrazone derivatives of isoxazolo[4,5-d] pyridazin-4(5H)-ones, Eur. J. Med. Chem., 45 (2010) 2345-2352.
G. Palla, G. Predieri, P. Domiano, Conformational behaviour and E/Z isomerization of N-acyl and N-aroylhydrazones, Tetrahedron, 42 (1986) 3649- 3654.
T. Thongthoom, P. Promsuwan, C. Yenjai, Synthesis and cytotoxic activity of the heptaphylline and 7-methoxyheptaphylline series, Eur. J. Med. Chem, 46 (2011) 3755-3761.
S. Sinha, B.C. Pal, S. Jagadeesh, P.P. Banerhee, A. Bandyopadhaya, S. Bhattacharya, Mahanine inhibits growth and induces apoptosis in prostate cancer cells through the deactivation of akt and activation of caspases, The Prostate, 66 (2006) 1257-1265.
M.K. Roy, V. N. Thalang, G. Trakoontivakorn, K. Nakahara, Mechanism of mahanine-induced apoptosis in human leukemia cells (HL-60), Biochem. Pharm., 67 (2004) 41-51.
C. Ito, M. Itoigawa, K. Nakao, T. Murata, N. Kaneda, H. Furukawa, Apoptosis of HL-60 leukemia cells induced by carbazole alkaloids isolated from Murraya euchrestifolia, J. Nat. Med., 66 (2012) 357-361.
S. Sarkar, D. Dutta, S.K. Samanta, K. Bhattacharya, B.C. Pal, J. Li, K. Datta, C. Mandal, Oxidative inhibition of Hsp90 disrupts the super-chaperone complex and attenuates pancreatic adenocarcinoma in vitro and in vivo, Int. J. Cancer, 132 (2013) 695-706.
B.A. Khan, A. Abraham, S. Leelamma, Antioxidant effects of Curry leaf, Murraya koenigii and mustard seeds, Brassica juncea in rats fed with high fat diet, Indian J. Exp. Biol., 35 (1997) 148-150.
M. Chakrabarty, A.C. Nath, S. Khasnobis, M. Chakrabarty, Y. Konda, Y. Harigaya, K. Komiyama, Carbazole alkaloids from Murraya koenigii, Phytochemistry, 46 (1997) 751-755.
M. Fiebig, J.M. Pezzuto, D.D. Soejarto, A.D. Kinghorn, Koenoline, a further cytotoxic carbazole alkaloid from Murraya koenigii, Phytochemistry, 24 (1985) 3041-3043.
K. Hirata, C. Ito, H. Furukawa, M. Itoigawa, L.M. Cosentino, K.H. Lee, Substituted 7H-pyrido[4,3-c] carbazoles with potent anti-HIV activity, Bioorg. Med. Chem. Lett., 9 (1999) 119-122.
M.T.H. Nutan, A.Hasnat, M.A. Rashid, Antibacterial and cytotoxic activities of Murraya koenigii, Fitoterapia, 69 (1998) 173-175.
Gürsoy, N. Karali, Synthesis and primary cytotoxicity evaluation of 3-[[(3-phenyl-4(3H)-quinazolinone-2-yl) mercaptoacetyl]hydrazono]-1H-2-indolinones, Eur. J. Med. Chem., 38 (2003) 633-643.
N. Terzioğlu, A. Gürsoy, Synthesis and anticancer evaluation of some new hydrazone derivatives of 2,6-dimethylimidazo[2,1-b]-[1,3,4]thiadiazole-5- carbohydrazide, Eur. J. Med. Chem., 38 (2003) 781- 786.
S.A.M. El-Hawash, A.E. Abdel Wahab, M.A. ElDewellawy, Cyanoacetic acid hydrazones of 3- (and 4-) acetylpyridine and some derived ring systems as potential antitumor and anti-HCV agents, Arch. Pharm. Chem. Life Sci., 339 (2006) 14-23.
N. Demirbas, S. Karaoglu, A. Demirbas, K. Sancak, Synthesis and antimicrobial activities of some new 1-(5-phenylamino-[1,3,4]thiadiazol-2-yl)methyl-5- oxo-[1,2,4]triazole and 1-(4-phenyl-5- thioxo-[1,2,4] triazol-3-yl)methyl-5-oxo-[1,2,4]triazole derivatives, Eur. J. Med. Chem., 39 (2004) 793-804.
B.N. Swamy, T.K. Suma, G.V. Rao, G.C. Reddy, Synthesis of isonicotinoylhydrazones from anacardic acid and their in vitro activity against Mycobacterium smegmatis, Eur. J. Med. Chem., 42 (2007) 420-424.
J. Pandey, R. Pal, A. Dwivedi, K. Hajela, Synthesis of some new diaryl and triaryl hydrazone derivatives as possible estrogen receptor modulators, Arzneimittelforschung., 52 (2002) 39-44.
15. H. Zhang, J. Drewe, B. Tseng, S. Kasibhatla, S.X. Cai, Discovery and SAR of indole-2-carboxylic acid benzylidenehydrazides as a new series of potent apoptosis inducers using a cellbased HTS assay, Bioorg. Med. Chem., 12 (2004) 3649-3655.
S.G. Küçükgüzel, A. Mazi, F. Sahin, S. Oztürk, J. Stables, Synthesis and biological activities of diflunisal hydrazide-hydrazones, Eur. J. Med. Chem., 38 (2003) 1005-1013.
D.G. Rando, D.N. Sato, L. Siqueira, A. Malvezzi, C.Q. F. Leite, A.T. Amaral, Potential tuberculostatic agents. Topliss application on benzoic acid [(5-nitro-thiophen2-yl)-methylene]-hydrazide series, Bioorg. Med. Chem., 10 (2002) 557-560.
B.K. Kaymakçıoğlu, S. Rollas, Synthesis, characterization and evaluation of antituberculosis activity of some hydrazones, Farmaco, 57 (2002) 595-599.
S.G. Küçükgüzel, S. Rollas, I. Küçükgüzel, M. Kiraz, Synthesis and antimycobacterial activity of some coupling products from 4-aminobenzoic acid hydrazones, Eur. J. Med. Chem., 34 (1999) 1093-1100.
MT. Cocco, C. Congiu, V. Onnis, MC. Pusceddu, ML. Schivo, A. Logu, Synthesis and antimycobacterial activity of some isonicotinoylhydrazones, Eur. J. Med. Chem., 34 (1999) 1071-1076.
Walcourt, M. Loyevsky, D.B. Lovejoy, V.R. Gordeuk, D.R. Richardson, Novel aroylhydrazone and thiosemicarbazone iron chelators with anti-malarial activity against chloroquine-resistant and -sensitive parasites, Int. J. Biochem. Cell Biol., 36 (2004) 401- 407.
J. Jayabharathi, A. Thangamani, M. Padmavathy, B. Krishnakumar, Synthesis and microbial evaluation of novel N(1)-Arilidene-N(2)-t(3)-methyl-r(2), c(6)-diarylpiperidin-4-one azine derivatives, Med. Chem. Res., 15 (2007) 431-442.
A.G.M. Fraga, C.R. Rodrigues, A.L.P. Miranda, E.J. Barreiro, C.A.M. Fraga, Synthesis and pharmacological evaluation of novel heterocyclic acylhydrazone derivatives, designed as PAF antagonists, Eur. J. Pharm. Sci., 11 (2000) 285-290.
P. Vicini, F. Zani, P. Cozzini, I. Doytchinova, Hydrazones of 1,2-benzisothiazole hydrazides: synthesis, antimicrobial activity and QSAR investigations, Eur. J. Med. Chem., 37 (2002) 553-564.
A.R. Todeschini, A.L. Miranda, C.M. Silva, S.C. Parrini, E.J. Barreiro, Synthesis and evaluation of analgesic, antiinflammatory and antiplatelet properties of new 2- pyridylarylhydrazone derivatives, Eur. J. Med. Chem., 33 (1998) 189-199.
N. Ergenç, N.S. Günay, Synthesis and antidepressant evaluation of new 3-phenyl-5-sulfonamid indole derivatives, Eur. J. Med. Chem., 33 (1998) 143-148.
J. Ragavendran, D. Sriram, S. Patel, I. Reddy, N. Bharathwajan, J. Stables, Design and synthesis of anticonvulsants from a combined phthalimide-GABAanilide and hydrazone pharmacophore, Eur. J. Med. Chem., 42 (2007) 146-151.
J.R. Dimmock, S.C. Vashishtha, J.P. Stables, Anticonvulsant properties of various acetylhydrazones, oxamoylhydrazones and semicarbazones derived from aromatic and unsaturated carbonyl compounds, Eur. J. Med. Chem., 35 (2000) 241-248.