Synthesis and biological evaluation of some new 1,3,4-thiadiazole and 1,2,4-triazole derivatives from L-methionine as antituberculosis and antiviral agents

Yıl 2015, Cilt: 19 Sayı: 2, 88 - 102, 10.04.2015

Esra Tatar Şükriye Küçükgüzel Sevgi Karakuş Eric De Clercq Graciela Andrei Robert Snoeck Christophe Pannecouque Sinem Öktem-okullu Nihal Ünübol Tanıl Kocagöz Sadık Kalaycı Fikrettin Şahin İlkay Küçükgüzel

https://doi.org/10.12991/mpj.2015199639

Öz

Some novel 1,3,4-thiadiazole [5-8] and 1,2,4-triazole [9-12] derivatives carrying amino acid moiety were synthesized starting from L-methionine. 1,3,4-Thiadiazole and 1,2,4-triazole scaffolds were prepared by cyclocondensation of the corresponding thiosemicarbazide and finally converted to their thiourea derivatives. Structures of the synthesized compounds [4-12] were confirmed by IR, 1H-NMR and 13C-NMR spectral data and elemental analysis. Synthesized compounds were evaluated for their antiviral and antibacterial activity. Of the screened compounds, N-{3-(methylsulfanyl)-1-[5-(phenylamino)-1,3,4-thiadiazole-2-yl]propyl}benzamide [5] was identified as the most potent inhibitor of Influenza A H3N2 virus with an EC50value of 31.4 μM, which serves as a lead compound for prospective development. The antituberculosis activity screen of the synthesized compounds revealed 1-[4-(4-chloro-(3-trifluoromethyl)phenyl-3-[3-(methylsulfanyl)-1-(4-phenyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)propyl]thiourea [12] as the most active compound against M. tuberculosis H37Rv strain (MIC : 16 µg/mL).

Anahtar Kelimeler

Thioureas; 1, 3, 4-thiadiazoles; 1, 2, 4-triazoles; antiviral activity; influenza; antituberculosis activity

L-Metiyoninden hareketle elde edilen bazı yeni 1,3,4-tiyadiazol ve 1,2,4-triazol türevlerinin sentezi, antitüberküler ve antiviral etkilerinin değerlendirilmesi

Öz

Bu çalışma kapsamında, L-metiyonin’den hareketle bazı yeni
1,3,4-tiyadiazol [5-8] ve 1,2,4-triazol [9-12] türevi bileşikler
sentezlenmiştir. İlgili tiyosemikarbazit’in siklokondensasyonu
ile elde edilen 1,3,4-tiyadiazol ve 1,2,4-triazol bileşikleri, yeni
tiyoüre türevlerinin sentez başlangıç maddelerini de
oluşturmaktadır. Sentezlenen bileşiklerin [4-12] yapıları IR,
1H-NMR ve 13C-NMR spektroskopisi yöntemleriyle
aydınlatılmıştır. Elde edilen bileşikler antiviral ve
antibakteriyel etkinlikleri açısından değerlendirilmişlerdir.
N-{3-(Metilsülfanil)-1-[5-(fenilamino)-1,3,4-tiyadiazol-2-il]
propil}benzamit’in [5], Influenza A H3N2 virüsüne karşı EC50:
31.4 μM derişimde etkinlik gösterdiği saptanmış ve devam
eden çalışmalarda geliştirilmek üzere önder bileşik olarak
tanımlanmıştır. Antitüberküloz etki çalışmaları sonucunda
1-[4-(4-kloro-(3-trifluorometil)fenil]-3-[3-(metilsülfanil)-1-(4-
fenil-5-tiyokso-4,5-dihidro-1H-1,2,4-triazol-3-il)propil]
tiyoüre’nin [12] M. tuberculosis H37Rv suşuna karşı MİK :
30.88 µM derişimde etkinlik gösterdiği belirlenmiştir.

Anahtar Kelimeler

Tiyoüre, 1, 3, 4-tiyadiazol, 1, 2, 4-triazol, antiviral etki, influenza, antitüberküler etki

Kaynakça

• Küçükgüzel I, Tatar E, Küçükgüzel SG, Rollas S, De Clercq E. Synthesis of some novel thiourea derivatives obtained from 5-[(4-aminophenoxy)methyl]-4-alkyl/aryl-2,4-dihydro-3H- 1,2,4-triazole-3-thiones and evaluation as antiviral/anti-HIV and anti-tuberculosis agents. Eur J Med Chem 2008;43: 381-92.
• De Clercq E. In search of a selective antiviral chemotherapy. Clin Microbiol Rev 1997;10: 674-93.
• De Clercq E. Hamao Umezawa Memorial Award Lecture: “An Odyssey in the Viral Chemotherapy Field”. Int J Antimicrob Agents 2001;18: 309-28.
• De Clercq E. Antiviral drugs in current clinical use. J Clin Virol 2004;30: 115-33.
• Uckun FM, Mao C, Pendergrass S, Maher D, Zhu D, Tuel- Ahlgren L, Venkatachalam TK. N-[2-(1-cyclohexenyl)ethyl]- N’-[2-(5-bromopyridyl)]-thiourea and N’-[2-(1-cyclohexenyl) ethyl]-N’-[2-(5-chloropyridyl)]-thiourea as potent inhibitors of multidrug-resistant human immunodeficiency virus-1. Bioorg Med Chem Lett 1999;9: 2721-6.
• Mao C, Sudbeck EA, Venkatachalam TK, Uckun FM. Rational design of N-[2-(2,5-dimethoxyphenylethyl)]-N’-[2-(5- bromopyridyl)]-thiourea (HI-236) as a potent non-nucleoside inhibitor of drug-resistant human immunodeficiency virus. Bioorg Med Chem Lett 1999;9: 1593-8.
• Högberg M, Engelhardt P, Vrang L, Zhang H. Bioisosteric modification of PETT-HIV-1 RT-inhibitors: synthesis and biological evaluation. Bioorg Med Chem Lett 2000;10: 265-8.
• D’Cruz OJ, Venkatachalam TK, Uckun FM. Novel thiourea compounds as dual-function microbicides. Biol Reprod 2000;63: 196-205.
• Hunter R, Younis Y, Muhanji CI, Curtin TL, Naidoo KJ, Petersen M, Bailey CM, Basavapathruni A, Anderson KS. C-2-aryl O-substituted HI-236 derivatives as non-nucleoside HIV-1 reverse-transcriptase inhibitors. Bioorg Med Chem 2008;16: 10270-80.
• Venkatachalam TK, Sudbeck EA, Mao C, Uckun FM. Stereochemistry of halopyridyl and thiazolyl thiourea compounds is a major determinant of their potency as nonnucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg Med Chem Lett 2000;10: 2071-4.
• Giret MT, Kallas EG. GBV-C: state of the art and future prospects. Curr HIV/AIDS Rep 2012;9: 26-33.
• Grebely J, Tyndall MW. Management of HCV and HIV infections among people who inject drugs. Curr Opin HIV AIDS 2011;6: 501-7.
• Barnabas RV, Webb EL, Weiss HA, Wasserheit JN. The role of coinfections in HIV epidemic trajectory and positive prevention: a systematic review and meta-analysis. AIDS 2011; 25: 1559-73.
• Bloom JD, Di Grandi MJ, Dushin RG, Curran KJ, Ross AA, Norton EB, Terefenko E, Jones TR, Feld B, Lang SA. Thiourea inhibitors of herpes viruses. Part 1: bis-(aryl)thiourea inhibitors of CMV. Bioorg Med Chem Lett 2003;13: 2929-32.
• Di Grandi MJ, Curran KJ, Feigelson G, Prashad A, Ross AA, Visalli R, Fairhurst J, Feld B, Bloom JD. Thiourea inhibitors of herpesviruses. Part 3: Inhibitors of varicella zoster virus. Bioorg Med Chem Lett 2004;14: 4157-60.
• Bloom JD, Curran KJ, DiGrandi MJ, Dushin RG, Lang SA, Norton EB, Ross AA, O’Hara BM. Benzamide-containing aryl thiourea derivatives useful as inhibitors of herpes viruses. PCT Int Appl 2000; WO 2000034238 A1.
• van Zeijl M, Fairhurst J, Jones TR, Vernon SK, Morin J, LaRocque J, Feld B, O’Hara B, Bloom JD, Johann SV. Novel class of thiourea compounds that inhibit herpes simplex virus type 1 DNA cleavage and encapsidation: resistance maps to the UL6 gene. J Virol 2000;74: 9054-61.
• Newcomb WW, Brown JC. Inhibition of Herpes Simplex Virus Replication by WAY-150138: Assembly of Capsids Depleted of the Portal and Terminase Proteins Involved in DNA Encapsidation. J Virol 2002;76: 10084-8.
• Guarner J, Falcón-Escobedo R. Comparison of the pathology caused by H1N1, H5N1, and H3N2 influenza viruses. Arch Med Res 2009;40: 655-61.
• Hayden FG. Antivirals for influenza: historical perspectives and lessons learned. Antiviral Res 2006;71: 372-8.
• Toor JS, Singh S, Sharma A, Arora SK. Mycobacterium tuberculosis modulates the gene interactions to activate the HIV replication and faster disease progression in a co-infected host. PLoS One 2014;9: e106815.
• WHO Interim policy on collaborative TB/HIV activities. http://whqlibdoc.who.int/publications/2012/9789241503006_ eng_Annexes.pdf (accessed Nov 7, 2014).
• Dobrikov GM, Valcheva V, Nikolova Y, Ugrinova I, Pasheva E, Dimitrov V. Efficient synthesis of new (R)-2-amino-1- butanol derived ureas, thioureas and acylthioureas and in vitro evaluation of their antimycobacterial activity. Eur J Med Chem 2013;63: 468-73.
• Küçükgüzel İ, Küçükgüzel SG, Rollas S, Kiraz M. Some 3-thioxo/alkylthio-1,2,4-triazoles with a substituted thiourea moiety as possible antimycobacterials. Bioorg Med Chem Lett 2001;11: 1703-7.
• Sriram D, Yogeeswari P, Madhu K. Synthesis and in vitro antitubercular activity of some 1-[(4-sub)phenyl]-3-(4-{1- [(pyridinecarbonyl)hydrazono]ethyl}phenyl)thiourea. Bioorg Med Chem Lett 2006;16: 876-8.
• Sriram D, Yogeeswari P, Dinakaran M, Thirumurugan R. Antimycobacterial activity of novel 1-(5-cyclobutyl-1,3- oxazol-2-yl)-3-(sub)phenyl/pyridylthiourea compounds endowed with high activity toward multidrug-resistant Mycobacterium tuberculosis. J Antimicrob Chemother 2007;59: 1194-6.
• Bhowruth V. Brown AK, Reynolds RC, Coxon GD, Mackay SP, Minnikin DE, Besra GS. Symmetrical and unsymmetrical analogues of isoxyl; active agents against Mycobacterium tuberculosis. Bioorg Med Chem Lett 2006;16:4743-7.
• Bobesh KA, Renuka J, Jeankumar VU, Shruti SK, Sridevi JP, Yogeeswari P, Sriram D. Extending the N-linked aminopiperidine class to the mycobacterial gyrase domain: pharmacophore mapping from known antibacterial leads. Eur J Med Chem 2014; 85:593-604.
• Ananthan S, Faaleolea ER, Goldman RC, Hobrath JV, Kwong CD, Laughon BE, Maddry JA, Mehta A, Rasmussen L, Reynolds RC, Secrist JA 3rd, Shindo N, Showe DN, Sosa MI, Suling WJ, White EL. High-throughput screening for inhibitors of Mycobacterium tuberculosis H37Rv. Tuberculosis (Edinb) 2009;89: 334-53.
• Karakuş S, Rollas S. Synthesis and antituberculosis activity of new N-phenyl-N’-[4-(5-alkyl/arylamino-1,3,4-thiadiazole- 2-yl)phenyl]thioureas. Farmaco 2002;57: 577-81.
• Karakuş S, Küçükgüzel ŞG, Küçükgüzel İ, De Clercq E, Pannecouque C, Andrei G, Snoeck R, Şahin F, Bayrak ÖF. : Synthesis, antiviral and anticancer activity of some novel thioureas derived from N-(4-nitro-2-phenoxyphenyl)- methanesulfonamide. Eur J Med Chem 2009;44: 3591-5.
• Çıkla P, Küçükgüzel Ş.G., Küçükgüzel İ., Rollas S., De Clercq E., Pannecouque C, Andrei G, Snoeck R., Şahin F., Bayrak ÖF. Synthesis and evaluation of antiviral, antitubercular and anticancer activities of some novel thioureas derived from 4-aminobenzohydrazide hydrazones. Marmara Pharm J 2010; 14:13-20.
• Talath S, Gadad AK. Synthesis, antibacterial and antitubercular activities of some 7-[4-(5-amino-[1,3,4] thiadiazole-2-sulfonyl)-piperazin-1-yl]fluoroquinolonic derivatives. Eur J Med Chem 2006;41: 918-24.
• Oruç EE, Rollas S, Kandemirli F, Shvets N, Dimoglo AS. 1,3,4-thiadiazole derivatives. Synthesis, structure elucidation, and structure-antituberculosis activity relationship investigation. J Med Chem 2004;47: 6760-7.
• Foroumadi A, Soltani F, Jabini R, Moshafi MH, Rasnani FM. Antituberculosis agents X. Synthesis and evaluation of in vitro antituberculosis activity of 2-(5-nitro-2-furyl)- and 2-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,3,4-thiadiazole derivatives. Arch Pharm Res. 2004;27:502-6.
• Kandemirli F, Shvets N, Unsalan S, Küçükgüzel I, Rollas S, Kovalishyn V, Dimoglo A. The structure-antituberculosis activity relationships study in a series of 5-(4-aminophenyl)- 4-substituted-2,4-dihydro-3h-1,2,4-triazole-3-thione derivatives. A combined electronic-topological and neural networks approach. Med Chem 2006;2: 415-22.
• Banfi E, Scialino G, Zampieri D, Mamolo MG, Vio L, Ferrone M, Fermeglia M, Paneni MS, Pricl S. Antifungal and antimycobacterial activity of new imidazole and triazole derivatives. A combined experimental and computational approach. J Antimicrob Chemother 2006;58: 76-84.
• Tatar E, Küçükgüzel İ, De Clercq E, Şahin F, Güllüce M. Synthesis, characterization and screening of antimicrobial, antituberculosis, antiviral and anticancer activity of novel 1,3-thiazolidine-4-ones derived from 1-[2-(benzoylamino)-4- (methylthio)butyryl]-4-alkyl/arylalkyl thiosemicarbazides. Arkivoc 2008;14:191-210.
• Liu JZ, Song BA, Fan HT, Bhadury PS, Wan WT, Yang S, Xu W, Wu J, Jin LH, Wei X, Hu DY, Zeng S. Synthesis and in vitro study of pseudo-peptide thioureas containing α-aminophosphonate moiety as potential antitumor agents. Eur J Med Chem 2010;45: 5108-12.
• Pannecouque C, Daelemans D, De Clercq E. Tetrazolium- based colorimetric assay for the detection of HIV replication inhibitors: revisited 20 years later. Nat Protoc 2008;3: 427-34.
• Pauwels R, Balzarini J, Baba M, Snoeck R, Schols D, Herdewijn P, Desmyter J, De Clercq E. Rapid and automated tetrazolium-based colorimetric assay for the detection of anti- HIV compounds. J Virol Methods 1988;20:309-21.
• Popovic M, Sarngadharan MG, Read E, Gallo RC. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 1984;224: 497-500.
• Barré-Sinoussi F, Chermann JC, Nugeyre MT, Chamaret S, Grest J, Dauget C, Axler-Blin C, Vézinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983;220: 868-71.
• Miyoshi I, Taguchi H, Kobonishi I, Yoshimoto S, Ohtsuki Y, Shiraishi Y, Akagi T. TypeC-virus-producing cell lines derived from adult T cell leukaemia. Gann Monogr 1982;28: 219-28.
• De Clercq E, Descamps J, Verhelst G, Walker RT, Jones AS, Torrence PF, Shugar D. Comparative efficacy of antiherpes drugs against different strains of herpes simplex virus. J Infect Dis 1980;141: 563–74.
• De Clercq E. Antiviral and antimetabolic activities of neplanocins. Antimicrob Agents Chemother 1985;28: 84–9.
• De Clercq E, Holý A, Rosenberg I, Sakuma T, Balzarini J, Maudgal P. A novel selective broad-spectrum anti-DNA virus agent. Nature 1986;323: 464-7.
• Vanderlinden E, Göktas F, Cesur Z, Froeyen M, Reed ML, Russell CJ, Cesur N, Naesens L. Novel inhibitors of influenza virus fusion: structure-activity relationship and interaction with the viral hemagglutinin. J Virol 2010;84: 4277-88.
• Göktaş F, Vanderlinden E, Naesens L, Cesur N, Cesur Z. Microwave assisted synthesis and anti-influenza virus activity of 1-adamantyl substituted N-(1-thia-4-azaspiro[4.5]decan-4- yl)carboxamide derivatives. Bioorg Med Chem 2012;20: 7155-9.
• Gül HI, Sahin F, Gul M, Ozturk S, Yerdelen KO. Evaluation of antimicrobial activities of several mannich bases and their derivatives. Arch Pharm (Weinheim) 2005;338: 335-8.
• Us D, Gürdal E, Berk B, Öktem S, Kocagöz T, Çağlayan B, Aksan Kurnaz İ, Demir Erol D. 4H -Pyran-4-one derivatives: leading molecule for preparation of compounds with antimycobacterial potential. Turk J Chem 2009;33: 803-12.
• Berk B, Us D, Öktem S, Kocagöz ZT, Çağlayan B, Aksan Kurnaz İ, Demir Erol D. Molecular modeling and antimycobacterial studies of Mannich bases: 5-hydroxy-2- methyl-4H -pyran-4-ones. Turk J Chem 2011;35: 317-30.
• Akgün H, Karamelekoğlu İ, Berk B, Kurnaz İ, Sarıbıyık G, Öktem S, Kocagöz T. Synthesis and antimycobacterial activity of some phthalimide derivatives. Bioorg Med Chem 2012;20: 4149-54.