Synthesis and Biological Evaluation of 2-Aminothiazole Analogues of Nα-Protected Amino Acids

Document Type : Research Article

Authors

1 Department of Chemistry, Siddaganga Institute of Technology, B.H. Road, Tumakuru, Karnataka, INDIA

2 Department of Chemistry, REVA University, Rukmini Knowledge Park, Kattigenahalli, Yelahanka, Bangalore, Karnataka, INDIA

3 Department of Chemistry, Government First Grade College, B.H. Road, Tumkur, Karnataka, INDIA

Abstract

Synthesis of 2-amino-thiazoles from Nα-protected bromomethyl ketones obtained from Nα-protected diazomethyl ketones has been reported in this study.N-protected amino acids were converted to diazomethylketones using (Benzotriazol-1-yloxy) tris (dimethylamino) phosphonium hexafluorophosphate (BOP) as carboxylic acid activator and N-nitroso-N-methyl urea (NMU) as diazomethane source. Thus, prepared diazomethylketones were treated with aqueous HBr to get bromomethyl ketones in high yields. The 2-amino-thiazoles of protected-amino acids were prepared by sonicating the bromomethyl ketones with thiourea in acetone, using Hantzsch’s procedure. The products were obtained in good yields and were fully characterized. The purity of the synthesized compounds was analyzed by collecting the RP-HPLC data for two sets of compounds. Kirby Bauer well diffusion technique was employed to test the antibacterial activity of the compounds,
Boc-Arg-thiazole, Cbz-Asp-thiazole, Cbz-Trp-thiazole, Fmoc-Phe-thiazole, and Fmoc-Trp-thiazole. The test leads to the promising activity with Streptomycin sulfate as standard and the compound Fmoc-Phe-thiazole was susceptible to Staphylococcus aureus.

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Main Subjects

References

[1] Link A.J., Vink M.K.S., Tirell D.A., Presentation and Detection of Azide Functionality in Bacterial Cell Surface Proteins, J. Am. Chem. Soc., 126(34): 10598-10602 (2004).
[2] Himo F., Demko Z.P., Noodleman L., Density Functional Theory Study of the Intramolecular [2 + 3] Cycloaddition of Azide to Nitriles, J. Org. Chem., 68(23): 9076-9080 (2003).
[3] Clapp L.B., Katritzky A.R., “Advances in Heterocyclic Chemistry”, Academic Press: New York, 20: 65-116 (1976).
[4] Einsedeil J., Thomas C., Hubner H., Gmeiner P., Phenyloxazoles and Phenylthiazoles as Benzamide Bioisosteres/Synthesis and Dopamine Receptor Binding Profiles, Bioorg. Med. Chem. Lett.,10(17): 2041-2044 (2000).
[5] (a) Ali A., Al-Hassani R., Hussain D., Jabir M., Meteab H., Anti-Proliferative Activity and Tubulin Targeting of Novel Micro and Nanoparticles Complexes of 4-Amino-3-Thion-1,2,4-Triazole Derivatives, Nano. Biomed. Eng., 12(1):075-089 (2020).
(b) Chohan Z.H., Hanif M., Design, Synthesis, and Biological Properties of Triazole Derived Compounds and Their Transition Metal Complexes, J. Enzyme Inhib. Med. Chem., 25(5): 737–749 (2010).
[6] (a) Nair V.P., Anang S., Subramani C., Madhvi A., Bakshi K., Srivastava A., Nayak S.B., Kumar C.T.R., Surjit M., Endoplasmic Reticulum Stress Induced Synthesis of a Novel Viral Factor Mediates Efficient Replication of Genotype-1 Hepatitis E Virus, PLoS Pathog., 12(4):1–31  (2016). (b) Mohammed I., Kummetha I.R., Singh G., Sharova N., Lichinchi G., Dang J., Stevenson M., Rana T.M., 1,2,3-Triazoles as Amide Bioisosteres: Discovery of a New Class of Potent HIV-1 Vif Antagonists,  J. Med. Chem., 59(16):7677-7682 (2016).
[7] (a) Turan-Zitouni G., Kaplancikli Z.A., Erol K., Kilic F.S., Synthesis and Analgesic Activity of Some Triazoles and Triazolothiadiazines, Farmaco, 54(4):218–223 (1999). (b) Vijesh A.M., Isloor A.M., Shetty P., Sundershan S., Fun H.K., New Pyrazole Derivatives Containing 1,2,4-Triazoles and Benzoxazoles as Potent Antimicrobial and Analgesic Agents, Eur. J. Med. Chem., 62:410–415 (2013).
[8] (a) Kulaba N.¸ Tatar E., Özakpınar O.B., Özsavcı D., Pannecouque C., De Clercq E., Küçükgüzel I., Synthesis and Antiproliferative Evaluation of Novel 2-(4 H -1,2,4-Triazole-3-Ylthio) Acetamide Derivatives as Inducers of Apoptosis in Cancer Cells, Eur. J. Med. Chem., 121:58–70 (2016). (b) Holla B.S., Veerendra B., Shivanada M.K., Poojary B., Synthesis, Characterization and Anticancer Activity Studies on Some Mannich Bases Derived from 1,2,4-Triazoles, Eur. J. Med. Chem., 38:759–767 (2003). (c) Narsimha S., Kumar N.S., Swamy B.K., Reddy N.V., Hussain S.A., Rao M.S., Indole-2-Carboxylic Acid Derived Mono and Bis 1,4-Disubstituted 1,2,3-Triazoles: Synthesis, Characterization and Evaluation of Anticancer, Antibacterial, and DNA-Cleavage Activities, Bioorg. Med. Chem. Lett., 26(6):1639-1644 (2016).
[9] Popiołek L., Kosikowska U., Mazur L., Dobosz M., Malm A., Synthesis and Antimicrobial Evaluation of Some Novel 1,2,4-Triazole and 1,3,4-Thiadiazole Derivatives, Med. Chem. Res., 22: 3134–3147 (2013).
[10] (a) Paprocka R., Wiese M., Eljaszewicz A., Helmin-Basa A., Gzella A., Modzelewska-Banachiewicz B., Michalkiewicz J., Synthesis and Anti-Inflammatory Activity of New 1,2,4-Triazole Derivatives, Bioorg. Med. Chem. Lett., 25(13): 2664–2667 (2015). (b) Hussein M.A., Shaker R.M., Ameen M.A., Mohammed M.F., Synthesis, Anti-Inflammatory, Analgesic, and Antibacterial Activities of some Triazole, Triazolothiadiazole, and Triazolothiadiazine Derivatives, Arch. Pharm. Res., 34(8): 1239–1250 (2011). (c) Shafi S., Alam M.M., Mulakayala N., Mulakayala C., Vanaja G., Kalle A.M., Pallu R., Alam M.S., Synthesis of Novel 2-Mercapto Benzothiazole and 1,2,3-Triazole Based Bis-Heterocycles: Their Anti-Inflammatory and Anti-Nociceptive Activities, Eur. J. Med. Chem., 49: 324-333 (2012).
[11] (a) Guo-Qiang H., Li-Li H., Song-Qiang X., Wen-Long H., Design, Synthesis and Antitumor Activity of Asymmetric Bis(S-Triazole Schiff Bases) Bearing Functionalized Side-Chain, Chin. J. Chem., 26(6): 1145–1149 (2008). (b) Salerno L., Pittalà V., Romeo G., Modica M.N., Siracusa M.A., Di Gi-acomo C., Acquaviva R., Barbagallo I., Tibullo D., Sorrenti V., Evaluation of Novel Aryloxyalkyl Derivatives of Imidazole and 1,2,4-Triazole as Heme Oxygenase-1(HO-1) Inhibitors and Their Antitumor Properties, Bioorg. Med. Chem., 21(17): 5145–5153 (2013).
[12] (a) Chohan Z.H., Sumrra S.H., Metal Based Biologically Active Compounds: Design, Synthesis, and Antibacterial/Antifungal/Cytotoxic Properties of Triazole-Derived Schiff Bases and Their Oxovanadium (IV) Complexes, Eur. J. Med. Chem., 45(7):2739–2747 (2010). (b) Miceli M.H., Kauffman C.A., Isavuconazole: A New Broad-Spectrum Triazole Antifungal Agent,  Clin. Infect. Dis., 61(10): 1558-1565 (2015).
[13] (a) Gao F., Wang T., Xiao J., Huang G., Antibacterial Activity Study of 1,2,4-Triazole Derivatives, Eur. J. Med. Chem., 173: 274-281 (2019). (b) Chohan Z.H., Hanif M., Synthesis and Characterization of Biologically Active New Schiff Bases Containing 3-Functionalized 1,2,4-Triazoles and Their Zinc (II) Complexes: Crystal Structure of 4-Bromo-2-[(E)-(1H-1,2,4-Triazol-3-Ylimino)-Methyl]Phenol, Appl. Organomet. Chem., 25(10): 753–760 (2011).
[14] (a) Cui X.S., Jing C., Chai K.Y., Lee J.S., Quan Z.S., Synthesis and Anticonvulsant Evaluation of
3-Substituted-4-(4-Hexyloxyphenyl)-4H-1,2,4-Triazoles, Med. Chem. Res., 18: 49–58 (2009). (b) Ayati A., Emami S., Foroumadi A., The Importance of Triazole Scaffold in the Development of Anticonvulsant Agents, Eur. J. Med. Chem., 109: 380-392 (2016).
[15] Maeda R., Studies on the Synthesis and Analgesic and Anti-Inflammatory Activities of 2-Thiazolylamino- and 2-Thiazolyloxyarylacetic Acid Derivatives, Chem. Pharm. Bull., 31(10): 3424-3445 (1983).
[16] Davidson B.S., Ascidians: Producers of Amino Acid-Derived Metabolites, Chem. Rev., 93(5):1771-1791 (1993).
[17] Latif H., Muhammad Z., Rehman U.R., Naveed A., William W.G., David P.L., Synthesis and Antibacterial Activity of Bis 2-Amino-4-Phenyl-5-Thiazolyl Disulfides, Chem. Pharm. Bull., 55(7):1014-1017 (2007).
[18] Hantzsch A., Weber J. H., Ueber Verbindungen Des Thiazols (Pyridins Der Thiophenreihe), Berichte der Deutschenchemischen Gesellschaft, 20(2): 3118-3132 (1887).
[19] Meyers I., Tavares F.X., Oxidation of Oxazolines and Thiazolines to oxazoles and Thiazoles: Application of the Kharasch-Sosnovsky Reaction, J. Org. Chem., 61(23):8207-8215 (1996).
[20] Moody C.J., Bagley M.C., Total Synthesis of (+)-Nostocyclamide, J. Chem. Soc. Perkin Trans. 1, (3):601-608 (1998).
[21] Kelly R.C., Gebhard I., Wicnienski N., Synthesis of (R)- and (S)-(Glu)Thz and the Corresponding Bisthiazole Dipeptide of Dolastatin, J. Org. Chem., 51(24): 4590-4594 (1986).
[22] Atkins G.M., Burgess E.M., The Reactions of an N-Sulfonylamine Inner Salt, J. Am. Chem. Soc., 90(17): 4744-4745 (1968).
[23] Lalithamba H.S., Narendra N., Naik S.A., Sureshbabu V.V., Ultrasound Mediated Synthesis of 2-Amino-1,3-Selenazoles Derived from Fmoc/Boc/Z-α-Amino Acids, ARKIVOC, (XI):77-90 (2010).
[24] Reeder M.R., Anderson R.M., α-Aminoalkyl- α′-Halomethylketones: Preparation and Application to Pharmaceutically Interesting Compounds, Chem. Rev., 106(7): 2828−2842 (2006).
[25] Nishimoto K., Ito M., Natori S., Ohmoto T., The Structure of Arundoin, the Triterpene Methyl Ether from Imperata Cylindrical Varmedia and Arundo Conspicua, Tetrahedron Lett., 6(27): 2245-2251 (1995).
[26] Gordon E.M., Godfrey J.D., Pluscec, J., Longen D.V., Natarajan S., Design of Peptide Derived Amino Alcohols as Transition-State Analog Inhibitors of Angiotensin Converting Enzyme, Biochem. Biophys. Res. Commun., 126(1): 419-426 (1985).
[27] Luly J.R., Plattner J.J., Herman S., New Y., Soderquist J., Marcotte P.A., Kleinert H.D., Perun T.J., Modified Peptides Which Display Potent and Specific Inhibition of Human Rennin, Biochem. Biophys. Res. Commun., 143(1): 44-51 (1987).
[28] Ullman B.R., Aja T., Deckwerth T.L., Diaz J.L., Herrmann J., Kallish V.J., Karanewsky D.S., Meduna S.P., Nalley K., Robinson E.D., Roggo S.P., Sayers R.O., Schmitz A., Ternansky R.J., Tomaselli K.J., Wu J.C., Structure–Activity Relationships within a Series of Caspase Inhibitors: Effect of Leaving Group Modifications, Bioorg. Med. Chem. Lett., 13(20): 3623-3626 (2003).
[29] Quibell M., Benn A., Flinn N., Tracy M., Manoj R., Yikang W., Watts J., Bicyclic Peptidomimetics Tetrahydrofuro[3,2-b]Pyrrol-3-One and Hexahydrofuro [3,2-b] Pyridine-3-One Based Scaffolds: Synthesis and Cysteinyl Proteinase Inhibition, Bioorg. Med. Chem., 12(21): 5689-5710 (2004).
[30] (a)  Noreen S., Sumrra S.H., Aminothiazole-Linked Metal Chelates: Synthesis, Density Functional Theory, and Antimicrobial Studies with Antioxidant Correlations, ACS Omega,  6: 33085−33099 (2021). (b) Sumrra S.H., Arshad Z., Zafar W., Mahmood K., Ashfaq M., Ul Hassa A., Mughal E.U., Irfan A., Imran M., Metal Incorporated Amino Thiazole-Derived Compounds: Synthesis, Density Function theory Analysis, in Vitro Antibacterial and Antioxidant Evaluation, R. Soc. Open Sci.,  8(9): 210910 (2021).
[31] (a) Zafar W., Sumrra S.H., Chohan Z.H., A Review: Pharmacological Aspects of Metal Based 1,2,4-Triazole Derived Schiff Bases, Eur. J. Med. Chem., 222:113602-113644 (2021). (b) Sumrra S.H., Zafar W., Imran M., Chohan Z.H., A Review on the Biomedical Efficacy of Transition Metal Triazole Compounds,
J. Coord. Chem., 75(3-4): 293-334 (2022).
(c) Sumrra S.H., Sahrish I., Raza M.A., Ahmad Z., Zafar M.N., Chohan Z.H., Ahmed S., Efficient Synthesis, Characterization, and in Vitro Bactericidal Studies of Unsymmetrically Substituted Triazole-Derived Schiff Base Ligand and its transition Metal Complexes, Monat. Für. Chemi -Chemical Monthly,  151: 549–557 (2020). (d) Sumrra S.H., Suleman A., Chohan Z. H., Zafar M. N., Raza M. A.,  Iqbal T., Triazole Metal Based Complexes as Antibacterial/Antifungal Agents, Russian J. Gen. Chem., 87(6): 1281–1287 (2017). (e)  Sumrra S.H., Zafar W., Javed H., Zafar M., Hussain M.Z., Imran M., Nadeem M.A., Facile Synthesis, Spectroscopic Evaluation and Antimicrobial Screening of Metal Endowed Triazole Compounds, BioMetals, 34:1329–1351 (2021)
[32] Bauer, A.W., Kirby, W. M., Sherris, J. C., TurckM., Antibiotic susceptibility Testing by a Standardized Single Disk Method, Am. J. Clin. Path., 45(4): 493-496 (1966).
Iranian Journal of Chemistry and Chemical Engineering
Volume 42, Issue 8 - Serial Number 130
August 2023
Pages 2494-2504

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