DFT Treatment of Some Cantharidine Isomers and Some Radicals from Them
Cantharidine (cantharidin) has been used as a medicine for centuries for many purposes. It is also known for its anticancer properties. In the present study, some cantharidine isomers and some radicals from them are considered within the realm of density functional theory. The isomers have been subjected to B3LYP/6-311++G(d,p) level of theory and the radicals from them are treated at the level of UB3LYP/6-31+G(d) level. The isomers considered are stereoisomers having the methyl groups at different stereo orientation. The calculations have revealed that the isomers are all thermally favorable and electronically stable. In each case, the mono radical formed from the isomer considered by the homolytic cleavage of C-H bond at the α-position of the etheric oxygen atom. These radicals are also thermally favorable and electronically stable. Various calculated properties of the isomers and the radicals have been harvested and discussed.
Oaks, W.W., Di Tunno, J.F., Magnani, T., Levy, H.A., & Mills, L.C. (1960). Cantharidine poisoning. Arch. Intern. Med., 105, 574-582. https://doi.org/10.1001/archinte.1960.00270160072009
Wang, G.S. (1989). Medical uses of mylabris in ancient China and recent studies. J. Ethnopharmacol., 26, 147-162. https://doi.org/10.1016/0378-8741(89)90062-7
Galvis, C.E.P., Mendez, L.Y.V., & Kouznetsov, V.V. (2013). Cantharidine-based small molecules as potential therapeutic agents. Chem. Biol. Drug Des., 82, 477. https://doi.org/10.1111/cbdd.12180
Gbaguidi, F.A., Kasséhin, U.C., Prevost, J.R.C., Frederick, R., McCurdy, C.R., & Poupaert, J.H. (2015). Insight into the Diels-Alder reaction: A green chemistry revisitation of the synthesis of a cantharidine-like trypanocidal pilot-molecule. Journal of Chemical and Pharmaceutical Research, 7(7), 1109-1113.
Khan, R.A., Rashid, M., & Naveed, M. (2022). Cantharidin: A chemical precursor for the development of novel bioinsecticides. Bulgarian Chemical Communications, 54(1), 19-28. https://doi.org/10.34049/bcc.54.1.5447
Deng, L.P., Dong, J., Cai, H., & Wang, W. (2013). Cantharidin as an antitumor agent: A retrospective review. Current Medicinal Chemistry, 20, 159-166.
Peng, F., Wei, Y.Q., Tian, L., Yang, L., Zhao, X., Lu, Y., Mao, Y.Q., Kan, B., Lei, S., Wang, G.S., Jiang, Y., Wang, Q.R., Luo, F., Zou, L.Q., & Liu, J.Y.J. (2002). Induction of apoptosis by norcantharidin in human colorectal carcinoma cell lines: involvement of the CD95 receptor/ligand. Cancer Res. Clin. Oncol., 128, 223-230. https://doi.org/10.1007/s00432-002-0326-5
Chen, Y.J., Kuo, C.D., Tsai, Y.M., Yu, C.C., Wang, G.S., & Liao, H.F. (2008). Norcantharidin induces anoikis through Jun-N-terminal kinase activation in CT26 colorectal cancer cells. Anti-Cancer Drugs, 19, 55-64. https://doi.org/10.1097/CAD.0b013e3282f18826
Chen, Y.N., Chen, J.C., Yin, S.C., Wang, G.S., Tsauer, W., Hsu, H.F., & Hsu, S.L. (2002). Effector mechanisms of norcantharidin-induced mitotic arrest and apoptosis in human hepatoma cells. Int. J. Cancer, 100, 158-165. https://doi.org/10.1002/ijc.10479
Williams, L.A., Moller, W., Merisor, E., Kraus, W., & Rosner, H. (2003). In vitro antiproliferation/cytotoxic activity of cantharidin (Spanish fly) and related derivatives. West. Ind. Med. J., 52, 10-13. PMID: 12806747.
Huh, J.E., Kang, K.S., Chae, C., Kim, H.M., Ahn, K.S., & Kim, S.H. (2004). Roles of p38 and JNK mitogen-activated protein kinase pathways during cantharidin-induced apoptosis in U937 cells. Biochem. Pharmacol., 67, 1811-1818. https://doi.org/10.1016/j.bcp.2003.12.025
Wu, J.Z., Situ, Z.Q., Chen, J.Y., Liu, B., & Wang, W. (1992). Chemosensitivity of salivary gland and oral cancer cell lines. Chin. Med. J., 105, 1026-1028.
Kok, S.H., Chui, C.H., Lam, W.S., Chen, J., Tang, J.C., Lau, F.Y., Cheng, G.Y., Wong, R.S., & Chan, A.S. (2006). Apoptotic activity of a novel synthetic cantharidin analog on hepatoma cell lines. Int. J. Mol. Med., 17, 945-949. https://doi.org/10.3892/ijmm.17.5.945
Kok, S.H., Chui, C.H., Lam, W.S., Chen, J., Tang, J.C., Lau, F.Y., Cheng, G.Y., Wong, R.S., & Chan, A.S. (2006). Apoptogenic activity of a synthetic cantharimide in leukaemia: implication on its structural activity relationship. Int. J. Mol. Med., 18, 1217-1221. https://doi.org/10.3892/ijmm.18.6.1217
Li, W., Xie, L., Chen, Z., Zhu, Y., Sun, Y., Miao, Y., Xu, Z., & Han, X. (2010). Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stress independent growth inhibition of pancreatic cancer cells through G2/M cellcycle arrest and apoptosis. Cancer Sci., 101, 1226-1233. https://doi.org/10.1111/j.1349-7006.2010.01523.x
Recanati, M.A., Kramer, K.J., Maggio, J.J., & Chao, C.R. (2018). Cantharidin is superior to trichloroacetic acid for the treatment of non-mucosal genital warts: A pilot randomized controlled trial, Clin. Exp. Obstet. Gynecol., 45(3), 383-386. https://doi.org/10.12891/ceog4112.2018
Coloe, J., & Morrell, D.S. (2009). Cantharidin use among pediatric dermatologists in the treatment of Molluscum Contagiosum, Pediatric Dermatology, 26(4), 405-408. https://doi.org/10.1111/j.1525-1470.2008.00860.x
Torbeck, R., Pan, M., de Moll, E., & Levitt, J. (2014). Cantharidin: a comprehensive review of the clinical literature, Dermatology Online Journal, 20(6). https://doi.org/10.5070/d3206022861
Stewart, J.J.P. (1989). Optimization of parameters for semi empirical methods I. J. Comput. Chem., 10, 209-220. https://doi.org/10.1002/jcc.540100208
Stewart, J.J.P. (1989). Optimization of parameters for semi empirical methods II. J. Comput. Chem., 10, 221-264. https://doi.org/10.1002/jcc.540100209
Leach, A.R. (1997). Molecular modeling. Essex: Longman.
Kohn, W., & Sham, L.J. (1965). Self-consistent equations including exchange and correlation effects. Phys. Rev., 140, 1133-1138. https://doi.org/10.1103/PhysRev.140.A1133
Parr, R.G., & Yang, W. (1989). Density functional theory of atoms and molecules. London: Oxford University Press.
Becke, A.D. (1988). Density-functional exchange-energy approximation with correct asymptotic behavior. Phys. Rev. A, 38, 3098-3100. https://doi.org/10.1103/PhysRevA.38.3098
Vosko, S.H., Wilk, L., & Nusair, M. (1980). Accurate spin-dependent electron liquid correlation energies for local spin density calculations: a critical analysis. Can. J. Phys., 58, 1200-1211. https://doi.org/10.1139/p80-159
Lee, C., Yang, W., & Parr, R.G. (1988). Development of the Colle-Salvetti correlation energy formula into a functional of the electron density. Phys. Rev. B, 37, 785-789. https://doi.org/10.1103/PhysRevB. 37.785
SPARTAN 06 (2006). Wavefunction Inc. Irvine CA, USA.
March, J. (1968). Advanced organic chemistry. Tokyo: McGraw-Hill Kogakusha.
Watkins, J.M., Mushrush, G.W., Hazlett, R.N., & Beal, E.J. (1989). Hydroperoxide formation and reactivity in jet fuels. Energy Fuels, 3, 231-6. https://doi.org/10.1021/ef00014a018
Mushrush, G.W., Beal, E.J., Hughes, J.M., Bonde, S.E., Gore, W.L., & Dolbear, G.E. (2002). Stability studies of a jet fuel containing no organo-sulfur compounds. Pet. Sci. Technol., 20(5-6), 561-70. https://doi.org/10.1081/LFT-120003580
Fodor, G.E., Naegeli, D.W., & Kohl, K.B. (1988). Peroxide formation in jet fuels. Energy Fuels, 2(6), 729-34. https://doi.org/10.1021/ef00012a002
Black, B.H., Hardy, D.R., & Beal, E.J. (1991). Accelerated hydroperoxide formation in jet fuel at 65 C in capped and vented bottles. Energy Fuels, 5(2), 281-2. https://doi.org/10.1021/ef00026a010
Zabarnick, S., & Phelps, D.K. (2006). Density functional theory calculations of the energetics and kinetics of jet fuel autoxidation reactions. Energy Fuels, 20(2), 488-97. https://doi.org/10.1021/ef050348l
Türker, L., Varis, S., & Bayar, Ç,Ç. (2013). A theoretical study of JP-10 hydroperoxidation. Fuel, 104, 128-132. https://doi.org/10.1016/j.fuel.2012.09.024
Hehre, W.J, Shusterman, A.J., & Huang, W.W. (1998). A laboratory book of computational organic chemistry. Irving, CA: Wavefunction.
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