4-Halo-N-(5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)benzamide and Benzothioamide Derivatives: Synthesis and in vitro Anticancer Assessment

Document Type : Research Article

Authors

1 Pharmaceutical Sciences Research Center, Health Institute, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, I.R. IRAN

2 Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, I.R. IRAN

Abstract

Cancer is a lethal disorder that has caused a serious threat to human health and nowadays there is a crucial need for the development of novel anticancer agents. A new series of 1,3,4-thiadiazole-based compounds were synthesized and evaluated for anti-cancer properties in vitro. The synthesis of 5-(Trifluoromethyl)-1,3,4-thiadiazol-2-amine (3) was carried out via solvent-free conditions and consequently, benzamide (4a-4f) and benzothioamide (5a-5f) derivatives bearing halogen moieties  (Cl, F) were synthesized. MTT assay was applied for in vitro cytotoxicity assessment against three cancerous cell lines consist of PC3 (Prostate cancer), HT-29 (Colon cancer), and SKNMC (Neuroblastoma). All tested derivatives exhibited equal or more (IC50 = 3-7 µM) cytotoxic activity than doxorubicin (IC50 = 7 µM) as a reference drug against PC3 cell line. Chlorine containing benzamideas well as benzothioamide derivatives (IC50 = 14-36 µM) were also exerted a higher cytotoxic activity against SKNMC cell line compared to doxorubicin (IC50 = 40 µM).

Keywords

Main Subjects

References

[1] Bhuva H.A., Kini S.G., Synthesis, Anticancer Activity and Docking of some Substituted Benzothiazoles
as Tyrosine Kinase Inhibitors, J. Mol. Graph.  Model., 29(1): 32-37 (2010).
[2] Kumar D., Patel G., Johnson E.O., Shah K., Synthesis and Anticancer Activities of Novel 3, 5-Disubstituted-1, 2, 4-Oxadiazoles, Bioorg. Med. Chem. Lett., 19(10): 2739-2741 (2009).
[3] Porter A.C., Vaillancourt R.R., Tyrosine Kinase Receptor-Activated Signal Transduction Pathways Which Lead to Oncogenesis, Oncogene., 17(11): 1343 (1998).
[4] Madhusudan S., Ganesan T.S., Tyrosine Kinase Inhibitors in Cancer Therapy, Clin  Biochem, 37(7): 618-635 (2004).
[5] Gupta J.K., Yadav R.K., Dudhe R., Sharma P.K., Recent Advancements in the Synthesis and Pharmacological Evaluation of Substituted 1, 3, 4-Thiadiazole Derivatives. Int. J. Pharm. Tech. Res., 2(2): 1493-1507 (2010).
[6] Kumar D., Vaddula B.R., Chang K-H., Shah K., One-Pot Synthesis and Anticancer Studies of 2-Arylamino-5-Aryl-1, 3, 4-Thiadiazoles, Bioorg. Med. Chem. Lett., 21(8): 2320-2323 (2010).
[7] Hosseinzadeh L, Khorand A, Aliabadi A. Discovery of 2‐Phenyl‐N‐(5‐(Trifluoromethyl)‐1, 3, 4‐Thiadiazol‐2‐Yl) Acetamide Derivatives as Apoptosis Inducers via the Caspase Pathway with Potential Anticancer Activity, Arch. Pharm., 346: 812-818 (2013).
[8] Rajak H., Deshmukh R., Aggarwal N., Kashaw S., Kharya M.D., Mishra P. Synthesis of Novel 2,
 5‐Disubstituted 1, 3, 4‐Thiadiazoles for Their Potential Anticonvulsant Activity: Pharmacophoric Model Studies, Arch.  Pharm., 342(8): 453-461 (2009).
[9] Abdel‐Aziz M., Aly O.M., Khan S.S., Mukherjee K., Bane S., Synthesis, Cytotoxic Properties And Tubulin Polymerization Inhibitory Activity of Novel 2‐Pyrazoline Derivatives, Arch. Pharm., 345(7): 535-548 (2012).
[10] Deng X.Q., Dong Z.Q., Song M.X., Shu B., Wang S.B., Quan Z.S., Synthesis and Anticonvulsant Activities of some Triazolothiadiazole Derivatives, Arch. Pharm., 345(7): 565-573 (2012).
[11] Rostom S.A., Badr M.H., Abd El Razik H.A., Ashour H., Abdel Wahab A.E., Synthesis of Some Pyrazolines and Pyrimidines Derived from Polymethoxy Chalcones As Anticancer and Antimicrobial Agents, Arch.  Pharm., 344(9): 572-587 (2011).
[12] Mishra G., Singh A.K., Jyoti K., Review Article on 1, 3, 4-Thiadiazole Derivatives And its Pharmacological Activities, Int. J. Chem. Tech. Res., 3: 1380-1393 (2011).
[13] Singh A.K., Mishra G., Jyoti K., Review on Biological Activities of 1, 3, 4-Thiadiazole Derivatives, J. App. Pharm. Sci., 5: 44-49 (2011).
[14] Kharb R., Kaur P., Sharma P.C., Yar M.S., Significance of Thiadiazole Derivatives as Antimicrobial Agents, Int. J. Res. Pharm. Biomed. Sci., 2(4): 1520-1540 (2011).
[15] Kalidhar U., Kaur A., 1, 3, 4-Thiadiazole Derivatives and Their Biological Activities: A Review, Res. J. Pharm. Biol. Chem., 4: 1091-1106 (2011).
[16] Siddiqui N., Ahuja P., Ahsan W., Pandeya S., Alam M.S., Thiadiazoles: Progress Report on Biological Activities, J. Chem. Pharm. Res., 1(1): 19-30 (2009).
[17] Farshori N.N., Banday M.R., Ahmad A., Khan A.U., Rauf A., Synthesis, Characterization, and in Vitro Antimicrobial Activities of 5-Alkenyl/Hydroxyalkenyl-2-Phenylamine-1, 3, 4-Oxadiazoles and Thiadiazoles, Bioorg.  Med.  Chem. Lett., 20(10): 1933-1938 (2010).
[18] Pattan S., Kekare P., Dighe N., Nirmal S., Musmade D., Parjane S., Daithankar A., Synthesis and Biological Evaluation of Some 1, 3, 4-Thiadiazoles, J. Chem.  Pharm. Res., 1(1): 191-198 (2009).
[19] Talath S., Gadad A., 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., 41(8): 918-924 (2006).
[20] Jatav V., Mishra P., Kashaw S., Stables J., CNS Depressant and Anticonvulsant Activities of Some Novel 3-[5-Substituted 1, 3, 4-Thiadiazole-2-Yl]-2-Styryl Quinazoline-4 (3H)-Ones, Eur. J. Med. Chem., 43(9): 1945-1954 (2008).
[21] Almajan G.L, Barbuceanu S-F., Bancescu G., Saramet I., Saramet G., Draghici C., Synthesis and Antimicrobial Evaluation of some Fused Heterocyclic [1, 2, 4] Triazolo [3, 4-B][1, 3, 4] Thiadiazole Derivatives, Eur.  J. Med. Chem., 45(12): 6139-6146 (2010).
[22] Noolvi M.N., Patel H.M., Singh N., Gadad A.K., Cameotra S.S., Badiger A., Synthesisand Anticancer Evaluation of Novel 2-Cyclopropylimidazo [2, 1-B] [1, 3, 4]-Thiadiazole Derivatives, Eur. J. Med. Chem., 46(9): 4411-4418 (2011).
[23] Supuran C.T., Scozzafava A., Carbonic Anhydrase Inhibitors-Part 94. 1, 3, 4-Thiadiazole-2-Sulfonamide Derivatives as Antitumor Agents?, Eur. J. Med. Chem., 35(9):867-874 (2009).
[24] Ibrahim D., Synthesis And Biological Evaluation of 3, 6-Disubstituted [1, 2, 4] Triazolo [3, 4-B][1, 3, 4] Thiadiazole Derivatives as a Novel Class of Potential Anti-Tumor Agents, Eur. J. Med. Chem., 44(7): 2776-2781(2009).
[25] Radi M., Crespan E., Botta G., Falchi F., Maga G., Manetti F., Corradi V., Mancini M., Santucci M.A., Schenone S., Botta M., Discovery and SAR of 1, 3, 4-Thiadiazole Derivatives as Potent Abl Tyrosine Kinase Inhibitors and Cytodifferentiating Agents, Bioorg. Med. Chem. Lett., 18(3): 1207-1211 (2008).
[26]Yang X-H., Wen Q., Zhao T-T., Sun J., Li X., Xing M., Lu X., Zhu H.-L., Synthesis, Biological Evaluation, And Molecular Docking Studies of Cinnamic Acyl 1, 3, 4-Thiadiazole Amide Derivatives as Novel Antitubulin Agents, Bioorg. Med. Chem., 20(3): 1181-1187 (2012).
[27] Sun J., Yang Y-S., Li W., Zhang Y-B., Wang X-L., Tang J-F., Zhu H.L., Synthesis, Biological Evaluation and Molecular Docking Studies of 1, 3, 4-Thiadiazole Derivatives Containing 1, 4-Benzodioxan as Potential Antitumor Agents, Bioorg. Med. Chem. Lett., 21(20): 6116-6121 (2011).
[28] Matysiak J., Opolski A., Synthesis and Antiproliferative Activity of N-Substituted  2-Amino-5-(2, 4-Dihydroxyphenyl)-1, 3, 4-Thiadiazoles, Bioorg. Med. Chem., 14(13): 4483-4489 (2006).
[29] Lalezari I., Sharghi N., Synthesis Of 1, 3, 4‐Thiadiazoles Containing the Trifluoromethyl Group, J.  Heterocycl.  Chem., 3(3): 336-337 (1966).
[30] Aliabadi A., Shamsa F., Ostad S.N., Emami S., Shafiee A., Davoodi J., Et Al., Synthesis and Biological Evaluation of 2-Phenylthiazole-4-Carboxamide Derivatives as Anticancer Agents, Eur. J. Med. Chem., 45(11): 5384-5389 (2011).
[31] Aliabadi A., Andisheh S., Tayarani-Najaran Z., Tayarani-Najaran M., 2-(4-Fluorophenyl)-N-Phenylacetamide Derivatives As Anticancer Agents: Synthesis and in-Vitro Cytotoxicity Evaluation, Iran.  J.  Pharm. Res., 12(3): 267-271 (2013).
[32] Nishio T., Sekiguchi H., Thionation of Ω-Hydroxy Amides with Lawesson's Reagent: Synthesis of Thioenamides and Sulfur-Containing Heterocycles, Tetrahedron., 55(16): 5017-5026 (1999).
[33] Burke M.J., Trantow B.M., An Efficient Route to 3-Aminoindazoles and 3-Amino-7-Azaindazoles, Tetrahedron. Lett., 49(31): 4579-4581 (2008).
[34] Aliabadi A., Afnanzade N., Hosseinzadeh L., Mohammadi-Farani A., Shafiee M.H., Nazari H., Ahmadi F., Foroumadi A., N-(5-(Trifluoromethyl)-1,3,4-Thiadiazol-2-Yl)Benzamide and Benzothioamide Derivatives Induce Apoptosis via Caspase-Dependent Pathway, Pharm. Chem. J., 53(6): 488-493 (2019).
Iranian Journal of Chemistry and Chemical Engineering
Volume 39, Issue 5 - Serial Number 103
September and October 2020
Pages 35-44

Files

Share

How to cite

Statistics