Tổng hợp các hợp chất 7-fluoro-3-substituted-1,2,4-triazolo[3,4-b]benzothiazoles (FTBs) mới như các tác nhân chống nấm mạnh: phân tích docking phân tử và đánh giá in silico

Research on Chemical Intermediates - Tập 42 - Trang 8329-8344 - 2016
Sharu Kukreja1, Anjali Sidhu1, Vineet K. Sharma2
1Department of Chemistry, Punjab Agricultural University, Ludhiana, India
2Department of Plant Pathology, Punjab Agricultural University, Ludhiana, India

Tóm tắt

Một loạt các hợp chất 1,2,4-triazolo[3,4-b]benzothiazoles có chứa fluor mới đã được tổng hợp bằng cách kết hợp dẫn xuất chống nấm đã được chứng minh 1,2,4-triazole với nhân benzothiazole chứa fluor, sử dụng chiến lược lai dẫn xuất. Các thử nghiệm chống nấm trong ống nghiệm đối với nhiều loại nấm gây bệnh thực vật cho thấy rằng nhóm aryl chlor hóa tại vị trí 3 của hệ thống liên hợp đã mang lại kết quả xuất sắc và đáng chú ý về độc tố nấm. Các hợp chất 3b và 3c được phát hiện là có tác dụng chống nấm tốt nhất đối với phần lớn các loại nấm thử nghiệm (giá trị EC50 thấp tới 0,24 mmoles/L) với kết quả tốt hơn hoặc tương đương với các tiêu chuẩn đã biết. Phân tích docking phân tử in silico và các chỉ số Lipinski phù hợp với xu hướng đã quan sát về hoạt động chống nấm. Hơn nữa, phân tích độ độc cho thấy các hợp chất thuộc lớp III về độ độc, tương tự như tiêu chuẩn được khuyến nghị.

Từ khóa

#chống nấm #fluorinated triazolo benzothiazoles #tổng hợp hợp chất #docking phân tử #độ độc

Tài liệu tham khảo

A. Sidhu, S. Kukreja, Synthesis of novel fluorinated benzothiazol-2-yl-1,2,4-triazoles: molecular docking, antifungal evaluation and in silico evaluation for SAR. Arab. J. Chem. (2015). doi:10.1016/j.arabjc.2015.01.009 Z. Rezaei, S. Khabnadideh, K. Pakshir, Z. Hossaini, F. Amiri, E. Assadpour, Design, synthesis, and antifungal activity of triazole and benzotriazole derivatives. Eur. J. Med. Chem. 44, 3064–3067 (2009) Y.S. Wu, H.K. Lee, S.F.Y. Li, High performance chiral separation of fourteen triazole fungicides by sulfated β-cyclodextrin-mediated capillary electrophoresis. J. Chromatogr. 912, 171–179 (2001) F. Bentiss, M. Lagrenee, M. Traisnel, J.C. Hornez, The corrosion inhibition of mild steel in acidic media by a new triazole derivative. Corros. Sci. 41, 789–803 (1999) H. Hof, Is there a serious risk of resistance development to azoles among fungi due to the widespread use and long-term application of azole antifungals in medicine? Drug Resist. Updat. 11, 25–31 (2008) M. Koparir, A. Cansiz, A. Demirdag, Synthesis of some new 4,5-substituted-4H-1,2,4-triazole-3-thiol derivatives. Molecules 9, 204–212 (2004) P. Naresh, P. Pattanaik, R.L. Priyadarshini, D.R. Reddy, Synthetic characterization & antimicrobial screening of some novel 6-fluorobenzothiazole substituted [1,2,4] triazole analogues. Int. J. Pharm. Res. Health Sci. 1, 18–24 (2013) X. Chai, J. Zhang, Y. Cao, Y. Zou, Q. Wu, D. Zhang, Y. Jiang, Q. Sun, Design, synthesis and molecular docking studies of novel triazole as antifungal agent. Eur. J. Med. Chem. 46, 3167–3176 (2011) T. Kumamoto, K. Toyooka, M. Nishida, H. Kuwahara, Y. Yoshimura, J. Kawada, S. Kubota, Effect of 2,4-dihydro-3H-1,2,4-triazole-3-thiones and thiosemicarbazones on iodide uptake by the mouse thyroid: the relationship between their structure and anti-thyroid activity. Chem. Pharm. Bull. 38, 2595–2596 (1990) I. Scholz, H. Oberwittler, K.D. Riedel, J. Burhenne, J. Weiss, W.E. Haefeli, G. Mikus, Pharmacokinetics, metabolism and bioavailability of the triazole antifungal agent voriconazole in relation to CYP2C19 genotype. Br. J. Clin. Pharmacol. 68, 906–915 (2009) H.A. Torres, R.Y. Hachem, R.F. Chemaly, D. Kontoyiannis, I.I. Raad, Posaconazole: a broad-spectrum triazole antifungal. Lancet Infect. Dis. 12, 775–785 (2005) W. Huang, G.F. Yang, Microwave-assisted, one pot synthesis and fungicidal activity of polyfluorinated 2-benzylthiobenzothiazoles. Bioorg. Med. Chem. 14, 8280–8285 (2006) K. Gumber, A. Sidhu, V. Kumar, Green synthesis of thiazol-2ylthiazolidin-4-ones as potential antifungals Russian. J. Appl. Chem. 88, 2065–2073 (2015) T.F. Abbs Fen Rejia, K.N. Rajasekharan, Synthesis of 2-[2,4-diaminothiazol-5-oyl]benzothiazoles. J. Heterocycl. Chem. 47, 994–997 (2010) C.P. Mpamhanga, D. Spinks, L.B. Tulloch, E.J. Shanks, D.A. Robinson, I.T. Collie, A.H. Fairlamb, P.G. Wyatt, J.A. Frearson, W.N. Hunter, I.H. Gilbert, R. Brenk, One scaffold, three binding modes: novel and selective pteridine reductase 1 inhibitors derived from fragment hits discovered by virtual screening. J. Med. Chem. 52, 4454–4465 (2009) G. Alang, R. Kaur, G. Kaur, A. Singh, P. Singla, Synthesis and antibacterial activity of some new benzothiazole derivatives. Acta Pharm. Sci. 52, 213–218 (2010) S.G. Kini, S. Choudhary, M. Mubeen, Synthesis, docking study and anticancer activity of coumarin substituted derivatives of benzothiazole. J. Comput. Methods Mol. Des. 2, 51–60 (2012) V.N. Telvekar, V.K. Bairwa, K. Satardekar, A. Bellubi, Novel 2-(2-(4-aryloxybenzylidene) hydrazinyl)benzothiazole derivatives as anti-tubercular agents. Bioorg. Med. Chem. Lett. 22, 649–652 (2012) C. Praveen, A. Nandakumar, P. Dheenkumar, D. Muralidharan, P.T. Perumal, Microwave-assisted one-pot synthesis of benzothiazole and benzoxazole libraries as analgesic agents. J. Chem. Sci. 124, 609–624 (2012) I. Hutchinson, S.A. Jennings, B.R. Vishnuvajjala, A.D. Westwell, M.F.G. Stevens, Synthesis and pharmaceutical properties of antitumor 2-(4-aminophenyl)benzothiazole amino acid prodrugs. J. Med. Chem. 45, 744–747 (2002) A. Rana, N. Siddiqui, S.A. Khan, Benzothiazoles: a new profile of biological activities Indian. J. Pharm. Sci. 69, 10–17 (2007) M. Ban, H. Taguchi, T. Katsushima, M. Takahashi, K. Shinoda, Novel antiallergic and antiinflammatory agents. Part I: synthesis and pharmacology of glycolic amide derivatives. Bioorg. Med. Chem 6, 1069–1076 (1998) D. Cressier, C. Prouillac, P. Hernandez, C. Amourette, M. Diserbo, C. Lion, G. Rima, Synthesis, antioxidant properties and radioprotective effects of new benzothiazoles and thiadiazoles. Bioorg. Med. Chem. 17, 5275–5284 (2009) J.C. Lee, M.D. Karve, U.S Patent 5,413,795. Chem. Abstr. (1995) W. Li, Q. Wu, Y. Ye, M. Luo, L. Hu, Y. Gu, F. Niu, J. Hu, Density functional theory and ab initio studies of geometry, electronic structure and vibrational spectra of novel benzothiazole and benzotriazole herbicides. Spectrochim. Acta Mol. Biomol. Spectros. 60, 2343–2354 (2004) A. Imramovsky, M. Pesko, J. Jampilek, K. Kralova, 1,3-Substituted imidazolidine-2,4,5-triones: synthesis and inhibition of cholinergic enzymes. Monatsh. Chem. 26, 1434–1440 (2014) T. Fujiwara, D.O. Hagan, Successful fluorine-containing herbicide agrochemicals. J. Fluorine Chem. 167, 16–29 (2014) L. Li, M. Li, H. Chi, J. Yang, Z. Li, C. Liu, Discovery of flufenoxystrobin: Novel fluorine-containing strobilurin fungicide and acaricide. J. Fluorine Chem. 185, 173–180 (2016) W. Jian, D. He, P. Xi, X. Li, Synthesis and biological evaluation of novel fluorine-containing stilbene derivatives as fungicidal agents against phytopathogenic fungi. J. Agric. Food Chem. 63(45), 9963–9969 (2015) M.N. Xanthopoulou, S.K. Hadjikakou, N. Hadjiliadis, M. Kubicki, S. Karkabounas, K. Haralabopoulos, N. Kourkoumelis, T. Bakas, Synthesis and characterization of a new chloro-di-phenyltin(IV) complex with 2-mercapto-nicotinic acid: study of its influence upon the catalytic oxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxtgenase. J. Organomet. Chem. 691, 1780–1789 (2009) S.S. Kaki, C. Grey, P. Adlercreutz, Bioorganic synthesis, characterization and antioxidant activity of esters of natural phenolics and α-lipoic acid. J. Biotech. 157(344–349), 40 (2012) A. Puratchikody, M. Doble, N. Ramalakshmi, Toxicity risk assessment of some novel quinoxaline fused thiazolidinones. J. Pharm. Res. 5, 340–342 (2012) K.P.S. Adinarayana, P.A. Reddy, P.A. Babu, Structural studies on docking selective COX-2 inhibitors. J. Bioinform. Res. 1, 21–26 (2012) S. Joginipelli, V.K. Melapu, J. Darsey, Combination of molecular modeling and quantum mechanical studies to understand quinolone resistance mechanism of mycobacterium tuberculosis austin. J. Comput. Biol. Bioinform. 1(2), 5 (2014) T.R. Devi, G.K.N. Chhetry, Evaluation of antifungal activities of certain plant against Fusarium udum Butler causing wilt in pigeonpea (Cajanus cajan (L.) Millsp.). Int. J. Sci. Res. Pub. 2, 1–4 (2012)