REVIEW OF BIOLOGICAL ACTIVITIES OF HYDRAZONES

Md. Rahmat Ali; Akranth Marella; Md. Tauquir Alam; Ruksar Naz; Mymoona Akhter; Md. Shaquiquzzaman; Rikta Saha; Omprakash Tanwar; Md. Mumtaz Alam; Jyoti Hooda

doi:10.14499/indonesianjpharm23iss4pp193-202

REVIEW OF BIOLOGICAL ACTIVITIES OF HYDRAZONES

Md. Rahmat Ali, Akranth Marella, Md. Tauquir Alam, Ruksar Naz, Mymoona Akhter, Md. Shaquiquzzaman, Rikta Saha, Omprakash Tanwar, Md. Mumtaz Alam, Jyoti Hooda

Abstract

Hydrazones possess an azomethine –NHN=CH group and are considered as derivatives of aldehydes and ketones in which the oxygen atom has been replaced by the NNH2 functional group. These are widely studied molecules owing to their ease of preparation and diverse pharmacological potential. This has led researchers to synthesize different heterocyclic compounds bearing hydrazones. Medicinal chemists across the world have done immense work on hydrazones and developed agents with better activity and low toxicity profiles. Following different synthetic protocols and through proper SAR studies differently substituted hydrazones have been developed and found to be active against different pharmcological targets. They are known to possess different biological activities viz. antimicrobial, antiinflammatory, anticancer, antimalarial etc. These observations have been guiding for the development of new hydrazones that possess varied biological activities. The review aims at highlighting the diverse biological activities of hydrazones.

Key words: Azomethine, Hydrazones, Pharmacological Potential

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References

Abdel-Wahab FB., Awad AEG., and Badria AF., 2011, Synthesis, antimicrobial, antioxidant, anti-hemolytic and cytotoxic evaluation of new imidazole-based heterocycles, Eur. J. Med. Chem., 46,

-1511.

Abdel-Wahab FB., Khidre ER. and Awad AEG. 2012, Regioselective synthesis and antimicrobial activities of some novel aryloxyacetic acid derivatives, Eur. J. Med. Chem., 50, 55-62.

Abu-Surrah AS., Safieh KAA., Ahmadb IM., Abdalla MY., Ayoub MT., Qaroush AK., and Abu-Mahtheieh AM. 2010, New palladium (II) complexes bearing pyrazole-based Schiff base ligands:

Synthesis, characterization and cytotoxicity, Eur. J. Med. Chem., 45, 471-475.

Ajani OO., Obafemi CA., Nwinyi OC., and Akinpelu DA. 2010, Microwave assisted synthesis and antimicrobial activity of 2-quinoxalinone-3-hydrazone derivatives, Bioorg. Med. Chem., 18, 214-221.

Ali A., Fisara P., Freemont JA., Kyi S., Meyer AG., Andrew G., Riches A.G., Sargent RM., Sawutz DG., Turner KA., Winzenberg KN., and Yang Q. 2010, Discovery of ectoparasiticidal hydrazono-trifluoromethanesulfonanilides, Bioorg. Med. Chem. Lett., 20, 649-652.

Al-Said MS., Bashandy MS., Al-qasoumi SI., and Ghorab MM., 2011, Anti-breast cancer activity of some novel 1,2-dihydropyridine, thiophene and thiazole derivatives, Eur. J. Med. Chem., 46, 137-141.

Aponte JC., Vaisberg AJ., Castillo D., Gonzalez G., Estevez Y., Arevalo J., Quiliano M., Zimic M., Verastegui M., Malaga E., Juan RHG., Bustamante B., Tarleton RL., Wang Y., Franzblau SG., Pauli GF., Sauvain M., and Hammond GB., 2010, Trypanoside, antituberculosis, leishmanicidal, and cytotoxic activities of tetrahydrobenzothienopyrimidines, Bioorg. Med. Chem., 18, 2880-2886.

Aslam MAS., Mahmood S., Shahid M Saeed A., and Iqbal J. 2011, Synthesis, biological assay in vitro and molecular docking studies of new Schiff base derivatives as potential urease inhibitors, Eur. J. Med. Chem., 46, 5473-5479.

Belskaya NP., Dehaen W., and Bakulev VA. 2010, Synthesis and properties of hydrazones bearing amide, thioamide and amidine functions, ARKIVOC, 1, 275-332.

Caputto ME., Fabian LE., Benitez D., Merlinoz A., Rios N., Cerecetto H., Moltrasio GY., Moglioni AG., Gonzalez, M., and Finkielsztein LM., 2011, Thiosemicarbazones derived from 1-indanones as new anti-Trypanosoma cruzi agents, Bioorg. Med. Chem., 19, 6818-6826.

Catto M., Aliano R., Carotti A., Cellamare S., Palluotto F., Purgatorio R., Stradis A.D., and Campagna F., 2010, Design, synthesis and biological evaluation of indane-2-arylhydrazinylmethylene-1,3-diones and indol aryldiazenylmethylene-3-ones as β-amyloid aggregation inhibitors, Eur. J. Med. Chem., 45, 1359-136.

Corey EJ., and Enders D., 1976, Applications of N,N-dimethylhydrazones to synthesis. cally selective CC bond formation, oxidative hydrolysis to carbonyl compounds, Tetrahedron Lett., 17, 3-6.

Corey EJ., and Enders D., 1976, Synthetic routes to polyfunctional molecules via metallated N,N-dimethylhydrazones, Tetrahedron Lett., 17, 11-14.

Cui Z., Li Y., Ling Y., Huang J., Cui J., Wang R., and Yang X., 2010, New class of potent antitumor acylhydrazone derivatives containing furan, Eur. J. Med. Chem., 45, 5576-5584.

de Oliveira KN., Costa P., Santin JR., Mazzambani L., Burger C., Mora C., Nunes RJ., and de-Souza MM., 2011, Synthesis and antidepressant-like activity evaluation of sulphonamides and sulphonyl-hydrazones, Bioorg. Med. Chem., 19, 4295-4306.

Edrees MM., Farghaly TA., El-Hag, AAF., Abdalla, M.M., 2010, Antimicrobial, antitumor and 5 α-reductase inhibitor activities of some hydrazonoyl substituted pyrimidinones, Eur. J. Med. Chem., 45, 5702-5707.

Effenberger K., Breyer S. and Schobert R. 2010, Modulation of doxorubicin activity in cancer cells by conjugation with fatty acyl and terpenyl hydrazones, Eur. J. Med. Chem., 45, 1947-1954.

El-Nakkady SS., Hanna MM., Roaiah HM., and Ghannam IAY., 2012, Synthesis, molecular docking study and antitumor activity of novel 2-phenylindole derivatives, Eur. J. Med. Chem., 47, 387-398.

El-Sabbagh OI., Shabaan MA., Kadry HH. and Al-Din ES. 2010, New octahydroquinazoline derivatives: Synthesis and hypotensive activity, Eur. J. Med. Chem., 45, 5390-5396.

El-Sayed MAA., Abdel-Aziz NI., Abdel-Aziz NAM., El-Azab AS., Asiri YA. and Tahir KEHE. 2011, Design, synthesis, and biological evaluation of substituted hydrazone and pyrazole derivatives as selective COX-2 inhibitors, molecular docking study, Bioorg. Med. Chem.,19, 3416-3424.

Eswaran S., Adhikari AV., Chowdhury IH., Pal, NK. and Thomas KD. 2010, New quinoline derivatives: Synthesis and investigation of antibacterial and antituberculosis properties, Eur. J. Med. Chem., 45, 3374-3383.

Fan CD., Su H., Zhao J., Zhao BX., Zhang SL. and Miao JY. 2010, A novel copper complex of salicylaldehyde pyrazole hydrazone induces apoptosis through up-regulating integrin β-4 in H322 lung carcinoma cells, Eur. J. Med. Chem., 45, 1438-1446.

Gage JL., Onrust R., Johnston D., Osnowski A., MacDonald W., Mitchell L., Urogdi L., Rohde A., Harbol K., Gragerov, S., Dorman G., Wheeler T., Florio V., and Cutshall NS., 2011, N-Acylhydrazones as inhibitors of PDE10A, Bioorg. Med. Chem. Lett., 21, 4155-4159.

Gouda MA., Berghot MA., Shoeib AI., and Khalil MA. 2010, Synthesis and antimicrobial of new anthraquinone derivatives incorporating pyrazole moiety, Eur. J. Med. Chem., 45, 1843-1848.

Govindasami T., Pandey A., Palanivelu N., and Pandey A., 2011, Synthesis, characterization and antibacterial activity of biologically important vanillin related hydrazone derivatives, Int. J. Org. Chem., 1, 71-77.

Hassan GS., Kadry HH., Abou-Seri SM., Ali, MM., and Mahmoud AEE., 2011, Synthesis and in vitro cytotoxic activity of novel pyrazolo[3,4-d]pyrimidines and related pyrazole hydrazones toward breast adenocarcinoma MCF-7 cell line, Bioorg. Med. Chem., 19, 6808-6817.

Hayat F., Salahuddin A., Zargan J. and Azam A. 2010, Synthesis, characterization, antiamoebic activity and cytotoxicity of novel 2-(quinolin-8-yloxy) acetohydrazones and their cyclized products (1,2,3-thiadiazole and 1,2,3-selenadiazole derivatives), Eur. J. Med. Chem., 45, 6127-6134.

Hernandez P., Cabrera M., Lavaggi ML., Celano L., Tiscornia I., da Costa TR., Thomson L., Bollati-Fogolin M., Miranda ALP., Lima LM., Barreirod E.J., Gonzalezd M. and Cerecettod H. 2012, Discovery of new orally effective analgesic and anti-inflammatory hybrid furoxanyl N-acylhydrazone derivatives, Bioorg. Med. Chem., 20, 2158-2171.

Isloor AM., Kalluraya B., and Pai KS., 2010, Synthesis, characterization and biological activities of some new benzo[b] thiophene derivatives, Eur. J. Med. Chem., 45, 825-830.

Jin CAY., Tan Z., He M., Tian B., Tang S., Hewlett,I., Yang, M., 2010, SAR and molecular mechanism study of novel acylhydrazone compounds targeting HIV-1, Bioorg. Med. Chem., 18, 2135-2140.

Jordao AK., Sathler PC., Ferreira VF., Campos VR., de Souza MCBV., Castro HC, H.C., Lannes A., Lourenco A., Rodrigues CR., Bello ML., Lourenco MCS., Carvalho GSL., Almeida MCB. and Cunha AC. 2011, Synthesis, antitubercular activity, and SAR study of N-substitutedphenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides, Bioorg. Med. Chem., 19, 5605-5611.

Jubie S., Meena S., Ramasheshu KV., Jawahar N. and Vijaykumar S. 2010, Synthesis and biological evaluation of some hydrazones and carbazones of indane 1,3-dione, Ind. J. Chem., 49B,1261-1263.

Kaushik D., Khan SA., Chawla G. and Kumar S. 2010, N’-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl) methylene] 2/4-substituted hydrazides: Synthesis and anticonvulsant activity, Eur. J. Med. Chem., 45, 3943-3949.

Kendall JD., Giddens AC., Tsang KY., Frederick R., Marshall ES., Singh R., Lill CL., Lee WJ., Kolekar S., Chao M., Malik A., Yu S., Chaussade C., Buchanan C., Rewcastle GW., Baguley BC., Flanagan JU., Jamieson SMF. and Denny WA. 2012, Shepherd, P.R., Novel pyrazolo[1,5-a] pyridines as p110α-selective PI3 kinase inhibitors: Exploring the benzenesulfonohydrazide SAR, Bioorg. Med. Chem., 20, 58-68.

Kumar D., Judge, V., Narang R., Sangwan S., Clercq DE., Balzarini J., and Narasimhan B., 2010, Benzylidene/2-chlorobenzylidene hydrazides: Synthesis, antimicrobial activity, QSAR studies and antiviral evaluation, Eur. J. Med. Chem., 45, 2806-2816.

Kumar D., Kumar NM., Ghosh S. and Shah K. 2012, Novel bis(indolyl)hydrazide–hydrazones as potent cytotoxic agents, Bioorg. Med. Chem. Lett., 22, 212-215.

Lee YJ., Jeong WK., Shin S., Lee UJ. and Kim Y. 2012, Discovery of novel selective inhibitors of Staphylococcus aureus β-ketoacyl acyl carrier protein synthase III, Eur. J. Med. Chem., 47, 261-269.

Maguene GM., Jakhlal J., Ladyman M., Vallin A., Ralambomanana DA., Bousquet T., Maugein J., Lebibi J., and Pelinski L., 2011, Synthesis and antimycobacterial activity of a series of ferrocenyl derivatives, Eur. J. Med. Chem., 46, 31-38.

Mahajan A., Kremer L., Louw S., Gueradel Y., Chibale, K., and Biot C., 2011, Synthesis and in vitro antitubercular activity of ferrocene-based hydrazones, Bioorg. Med. Chem. Lett., 21, 2866-2868.

Moldovan CM., Oniga O., Parvu A., Tiperciuc B., Verite P., Pirnau A., Bojit OCM. and Pop R. 2011, Synthesis and antiinflammatory evaluation of some new acyl-hydrazones bearing 2-aryl-thiazole,

Eur. J. Med. Chem., 46, 526-534.

Musad EA., Mohamed R., Saeed BA., Vishwanath BS. and Rai KML. 2011, Synthesis and evaluation of antioxidant and antibacterial activities of new substituted bis(1,3,4-oxadiazoles), 3,5-bis(substituted) pyrazoles and isoxazoles, Bioorg. Med. Chem. Lett., 21, 3536–3540.

Ozdemir A., Turan-Zitouni G., Kaplanciklia AZ., Iscan G., Khan S. and Demirci F. 2010, Synthesis and the selective antifungal activity of 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine derivatives, Eur. J. Med. Chem., 45, 2080-2084.

Ozkay Y., Tunali Y., Karaca H. and Isikdag I. 2010, Antimicrobial activity and a SAR study of some novel benzimidazole derivatives bearing hydrazone moiety, Eur. J. Med. Chem., 45, 3293-3298.

Pavan FR., Maia PIS., Leite SRA., Deflon VM., Batista AA., Sato DN., Franzblau S.G. and Leite CQF. 2010, Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/ hydrazones: Anti-Mycobacterium tuberculosis activity and cytotoxicity, Eur. J. Med. Chem., 45, 1898-1905.

Raja AS., Agarwal AK., Mahajan N., Pandeya, SN. and Ananthan A. 2010, Antibacterial and antitubercular activity of some diphenyl hydrazone and semicarbazone, Ind. J. Chem., 49B, 1384-1388.

Rajitha G., Saideepa N., Praneetha P., 2011, Synthesis and evaluation of N-(α-benzamidocinnamoyl)aryl hydrazone derivative for anti-inflammatory and antioxidant activities,Ind. J. Chem., 50B, 729-733.

Rane RA., and Telvekar VN.,2010 Synthesis and evaluation of novel chloropyrrole molecules designed by molecular hybridization of common pharmacophores as potential antimicrobial agents, Bioorg. Med. Chem. Lett., 20, 5681–5685.

Rasras MJA., Al-Tel HT., Al-Aboudi FA. and Al-Qawasmeh AR., 2010, Synthesis and antimicrobial activity of cholic acid hydrazone analogues, Eur. J. Med. Chem., 45, 2307-2313.

Rollas S., and Kucukguzel SG., 2007, Biological Activities of Hydrazone Derivatives. Molecules, 12, 1910-1939.

Romeiro NC., Aguirre G., Hernandez P., González M., Cerecetto H., Aldana I., Silanes SP., Monge A., Barreiro EJ. And Lima LM., 2009, Synthesis, trypanocidal activity and docking studies of novel quinoxaline-N-acylhydrazones, designed as cruzain inhibitors candidates, Bioorg. Med. Chem., 17, 641-652.

Sharma RN., Sharma KP. and Dikshit SN., 2011, Synthesis, Characterization and biological activities of some new hypophosphorousadducts of acid hydrazones derived from 2-[(N-benzoyl)

, 3 dichloroanilido] acetohydrazide, Archives of Applied Science Research, 3, 415-424

Siddiqui SM., Salahuddin A. and Azam A., 2012, Synthesis, characterization and antiamoebic activity of some hydrazone and azole derivatives bearing pyridyl moiety as a promising heterocyclic scaffold,Eur. J. Med. Chem., 49, 411-416.

Thomas KD., Adhikari, AV., Telkar S., Chowdhury, I.H., Mahmood, R., Pal, K.N., Rowd, G., Sumesh, E. 2011, Design, synthesis and docking studies of new quinoline-3-carbohydrazide derivatives as antitubercular agents, Eur. J. Med. Chem., 46, 5283-5292.

Uppal G., Bala S., Kamboj S., and Saini M., 2011, Therapeutic Review Exploring Antimicrobial Potential of Hydrazones as Promising Lead, Der Pharma Chemica, 3, 250-268.

Vaio MAFVD., Freitas ACC., Castro H.C., Albuquerque SD., Cabral LM., Rodrigues CR., Albuquerque MG., Martins RCA., Henriques MGMO., Dias and LRS., 2009, Synthesis, antichagasic

in vitro evaluation, cytotoxicity assays, molecular modeling and SAR/QSAR studies of a 2-phenyl-3-(1-phenyl-1Hpyrazol-4-yl)-acrylic acid benzylidenecarbohydrazide series, Bioorg. Med. Chem., 17, 295-302.

Vavrikova E., Polanc S., Kocevar M., Horvati K., Bosze S., Stolarikova J., Vavrova K. and Vinsova J., 2011, New fluorinecontaining hydrazones active against MDR-tuberculosis, Eur. J. Med. Chem., 46, 4937-4945.

Vijesh AM., Isloor MA., Prabhu V., Ahmad S., and Malladi S., 2010, Synthesis, characterization and anti-microbial studies of some novel 2,4-disubstituted thiazoles, Eur. J. Med. Chem., 45, 5460-5464.

DOI: http://dx.doi.org/10.14499/indonesianjpharm23iss4pp193-202