3,5-Disubstituted Isoxazole Derivatives: Potential Inhibitors of Inflammation and Cancer

详细信息    查看全文

• 作者：Kodagahalli Sathya Rakesh ; Swamy Jagadish…
• 关键词：3 ; 5 ; disubstituted isoxazoles ; lipoxygenase ; cyclooxygenase ; peritoneal angiogenesis ; inflammation ; carcinogenesis
• 刊名：Inflammation
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：39
• 期：1
• 页码：269-280
• 全文大小：3,281 KB
• 参考文献：1.Griga, T., A. Tromm, J. Spranger, and B. May. 1998. Increased serum levels of vascular endothelial growth-factor in patients with inflammatory bowel-disease. Scandinavian Journal of Gastroenterology 33: 504–508.CrossRef PubMed
  2.Nagashima, M., S. Yoshino, T. Ishiwata, and G. Asano. 1995. Role of vascular endothelial growth factor in angiogenesis of rheumatoid arthritis. The Journal of Rheumatology 22: 1624–1630.PubMed
  3.Hussain, S.P., L.J. Hofseth, and C.C. Harris. 2003. Radical causes of cancer. Nature Reviews Cancer 3: 276–285.CrossRef PubMed
  4.Hammamieh, R., D. Sumaida, X. Zhang, R. Das, and M. Jett. 2007. Control of the growth of human breast cancer cells in culture by manipulation of arachidonate metabolism. BMC Cancer 7: 138.PubMedCentral CrossRef PubMed
  5.Janne, P.A., and R.J. Mayer. 2000. Chemoprevention of colorectal cancer. The New England Journal of Medicine 342: 1960–1968.CrossRef PubMed
  6.Shaheen, N.J., W.L. Straus, and R.S. Sandler. 2002. Chemoprevention of gastrointestinal malignancies with non-steroidal anti-inflammatory drugs. Cancer 94: 950–963.CrossRef PubMed
  7.Thun, M.J., S.J. Henley, and C. Patrono. 2002. Nonsteroidal anti-inflammatory drugs as anticancer agents: Mechanistic, pharmacologic, and clinical issues. Journal of the National Cancer Institute 94: 252–266.CrossRef PubMed
  8.Basappa, K. Sugahara, K.N. Thimmaiah, H.K. Bid, P.J. Houghton, and K.S. Rangappa. 2012. Anti-tumor activity of a novel HS-mimetic-vascular endothelial growth factor binding small molecule. PLoS ONE 7, e39444.PubMedCentral CrossRef
  9.Gately, S. 2000. The contributions of cyclooxygenase-2 to tumor angiogenesis. Cancer Metastasis Reviews 19: 19–27.CrossRef PubMed
  10.Ding, X.Z., P. Iversen, M.W. Cluck, J.A. Knezetic, and T.E. Adrian. 1999. Lipoxygenase inhibitors abolish proliferation of human pancreatic cancer cells. Biochemical and Biophysical Research Communications 261: 218–223.CrossRef PubMed
  11.Coussens, L.M., and Z. Werb. 2002. Inflammation and cancer. Nature 420: 860–867.PubMedCentral CrossRef PubMed
  12.Hanahan, D., and J. Folkman. 1996. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86: 353–364.CrossRef PubMed
  13.Sumitani, K., R. Kamijo, T. Toyoshima, Y. Nakanishi, K. Takizawa, M. Hatori, and M. Nagumo. 2001. Specific inhibition of cyclooxygenase-2 results in inhibition of proliferation of oral cancer cell lines via suppression of prostaglandin E2 production. Journal of Oral Pathology & Medicine 30: 41–47.CrossRef
  14.Ding, X.Z., C.A. Kuszynski, T.H. El-Metwally, and T.E. Adrian. 1999. Lipoxygenase inhibition induced apoptosis, morphological changes, and carbonic anhydrase expression in human pancreatic cancer cells. Biochemical and Biophysical Research Communications 266: 392–399.CrossRef PubMed
  15.Ding, X.Z., W.G. Tong, and T.E. Adrian. 2001. 12-lipoxygenase metabolite 12(S)-HETE stimulates human pancreatic cancer cell proliferation via protein tyrosine phosphorylation and ERK activation. International Journal of Cancer Journal International Du Cancer 94: 630–636.CrossRef PubMed
  16.Form, D.M., and R. Auerbach. 1983. PGE2 and angiogenesis. Proceedings of the Society for Experimental Biology and Medicine 172: 214–218.CrossRef PubMed
  17.Hyde, C.A., and S. Missailidis. 2009. Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis. International Immunopharmacology 9: 701–715.CrossRef PubMed
  18.Lu, H., W. Ouyang, and C. Huang. 2006. Inflammation, a key event in cancer development. Molecular Cancer Research 4: 221–233.CrossRef PubMed
  19.Tsujii, M., and R.N. DuBois. 1995. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 83: 493–501.CrossRef PubMed
  20.Tsujii, M., S. Kawano, and R.N. DuBois. 1997. Cyclooxygenase-2 expression in human colon cancer cells increases metastaticpotential. Proceedings of the National Academy of Sciences of the United States of America 94: 3336–3340.
  21.Bartsch, H., and J. Nair. 2006. Chronic inflammation and oxidative stress in the genesis and perpetuation of cancer: Role of lipid peroxidation, DNA damage, and repair. Langenbeck's Archives of Surgery / Deutsche Gesellschaft fur Chirurgie 391: 499–510.CrossRef PubMed
  22.Herschman, H.R. 1996. Prostaglandin synthase 2. Biochimica et Biophysica Acta 1299: 125–140.CrossRef PubMed
  23.Thomsen, R., and M.H. Christensen. 2006. MolDock: a new technique for high accuracy molecular docking. Journal of Medicinal Chemistry 49: 3315–3321.CrossRef PubMed
  24.Raghava, B., G. Parameshwarappa, A. Acharya, T.R. Swaroop, K.S. Rangappa, and H. Ila. 2014. Cyclocondensation of hydroxylamine with 1,3-bis(het)arylmonothio 1,3-diketones and 1,3-bis(het)aryl-3-(methylthio)-2-propenones: Synthesis of 3,5-bis(het)arylisoxazoles with complementary regioselectivity. European Journal of Organic Chemistry 2014: 1882–1892.CrossRef
  25.Rakesh, K.S., S. Jagadish, T.R. Swaroop, N. Ashwini, K.B. Harsha, and K.S. Rangappa. 2014. Anti-oxidant and anti-inflammatory activities of synthetic 2,4-bis (aryl/heteroaryl)-5-acylthiazole derivatives. Asian Journal Bio and Pharm Research 4: 316–327.
  26.Sadashiva, M.P., M.P. Sadashiva, Basappa, S. NanjundaSwamy, F. Li, K.A. Manu, M. Sengottuvelan, D.S. Prasanna, N.C. Anilkumar, G. Sethi, K. Sugahara, and K.S. Rangappa. 2012. Anti-cancer activity of novel dibenzo[b,f]azepine tethered isoxazoline derivatives. BMC Chemical Biology 12: 1472.
  27.Chandrappa, S., H. Chandru, A.C. Sharada, K. Ananda Vinaya, C.S. Kumar, N.R. Thimmegowda, and K.S. Rangappa. 2010. Synthesis and in vivo anti-cancer and anti-angiogenic effects of novel thioxothiazolidin-4-one derivatives against transplantable mouse tumor. Medicinal Chemistry Research 19: 236–249.CrossRef
  28.Kumar, C.A., S. Basappa Jayarama, B.P. Salimath, and K.S. Rangappa. 2007. Pro-apoptotic activity of imidazole derivatives mediated by up-regulation of Bax and activation of CAD in Ehrlich Ascites Tumor cells. Investigational New Drugs 25: 343–350.CrossRef PubMed
  29.Gurupadaswamy, H.D., P. Thirusangu, B.R. Vijay Avin, V. Vigneshwaran, M.V. Prashanth Kumar, T.S. Abhishek, V. Lakshmi Ranganatha, S.A. Khanum, and B.T. Prabhakar. 2014. (2,5-Di(4-aryloylaryloxymethyl)-1,3,4-oxadiazole) exhibits p53 induced apoptogenesis through Caspase-3 mediated endonuclease activity in murine carcinoma. Biomedicine & Pharmacotherapy 68: 791–797.CrossRef
  30.Lakshmi Ranganatha, V., F. Zameer, S. Meghashri, N.D. Rekha, V. Girish, H.D. Gurupadaswamy, and S.A. Khanum. 2013. Design, synthesis, and anticancer properties of novel benzophenone-conjugated coumarin analogs. Archiv der Pharmazie 346: 901–911.CrossRef PubMed
  31.Schüttelkopf, A.W., and D.M.F.V. Aalten. 2004. PRODRG - a tool for high throughput crystallography of protein ligand complexes. Acta Crystallographic 68: 1355–1363.
  32.Schneider, C., and A. Pozzi. 2011. Cyclooxygenases and lipoxygenases in cancer. Cancer Metastasis Reviews 30: 277–294.PubMedCentral CrossRef PubMed
  33.Claria, J. 2006. Regulation of cell proliferation and apoptosis by bioactive lipid mediators. Recent Patents on Anti-Cancer Drug Discovery 1: 369–382.CrossRef PubMed
  34.De Vries, C.E., and C.J. Van Noorden. 1992. Effects of dietary fatty acid composition on tumor growth and metastasis. Anticancer Research 12: 1513–1522.PubMed
  35.Gupta, R.A., and R.N. Dubois. 2001. Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nature Reviews Cancer 1: 11–21.CrossRef PubMed
  36.Fosslien, E. 1998. Adverse effects of nonsteroidal anti-inflammatory drugs on the gastrointestinal system. Annals of Clinical and Laboratory Science 28: 67–81.PubMed
  37.Bresalier, R.S., R.S. Sandler, H. Quan, J.A. Bolognese, B. Oxenius, K. Horgan, C. Lines, R. Riddell, D. Morton, A. Lanas, M.A. Konstam, and J.A. Baron. 2005. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. The New England Journal of Medicine 352: 1092–1102.CrossRef PubMed
  38.Dogne, J.M., C.T. Supuran, and D. Pratico. 2005. Adverse cardiovascular effects of the coxibs. Journal of Medicinal Chemistry 48: 2251–2257.CrossRef PubMed
  
• 作者单位：Kodagahalli Sathya Rakesh (1)
  Swamy Jagadish (1)
  Kyathegowdanadoddi Srinivas Balaji (2)
  Farhan Zameer (3)
  Toreshettahally Ramesh Swaroop (1)
  Chakrabhavi Dhanajaya Mohan (1)
  Shankar Jayarama (2)
  Kanchugarakoppal Subbegowda Rangappa (1)
  
  1. Department of Studies in Chemistry, University of Mysore, Crawford Hall, Mysore, 570 006, Karnataka, India
  2. Department of Biotechnology, Terresian College, University of Mysore, Mysore, 570 011, Karnataka, India
  3. Department of Biotechnology, Biochemistry and Microbiology, Mahajana Research Foundation, SBRR Mahajana First Grade College, University of Mysore, JL Puram, Mysore, 570 012, Karnataka, India
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Rheumatology
  Internal Medicine
  Pharmacology and Toxicology
  Pathology
  
• 出版者：Springer Netherlands
• ISSN：1573-2576

文摘

The products of arachidonic acid metabolism by lipoxygenase (LOX) and cyclooxygenase (COX) significantly contribute to inflammation and carcinogenesis. Particularly, overproduction of leukotrienes and prostaglandins contribute to tumor growth by inducing formation of new blood vessels that sustain tumor cell viability and growth. Hence, search for novel anticancer drug via inhibition of LOX and COX enzymes constitutes an impressive strategy till date. In this context, a series of isoxazole derivatives were synthesized and screened for their anti-inflammatory activity via LOX and COX inhibition. Among these, 3-(3-methylthiophen-2-yl)-5-(3,4,5-trimethoxyphenyl)isoxazole (2b) showed significant inhibitory activity toward LOX and COX-2. Additionally, 2b showed a good inhibition of tumor growth, peritoneal angiogenesis, and ascite formation in Ehrlich ascites carcinoma (EAC) cell mouse model. Further, the in silico molecular studies also revealed that the compound 2b binds to the catalytic domain of LOX and COX-1 and COX-2 strongly with high atomic contact energy (ACE) score compared to standard drug. These initial pharmacological data support the fact that the compound 2b serves as the basis in developing anti-inflammatory and anticancer agents. KEY WORDS 3,5-disubstituted isoxazoles lipoxygenase cyclooxygenase peritoneal angiogenesis inflammation carcinogenesis