Photo-stability and Photo-reactivity of halogenated 8-methoxypsoralen, the basis for designing of new drugs
Abstract
8-methoxypsoralen is an efficient photosensitizer agent, used widely in PUVA therapy in treatment of different skin disorders like psoriasis, and other inflammatory skin disorders or recently in treatment of cancer diseases such as cutaneous T-cell lymphoma. Teen different substitutions of this compound have been made in this work, through fluorine and bromine atoms substitutions in order to increase its photosensitizer efficiency. In each system, we replace only one hydrogen atom of 8-methoxypsoralen by fluorine atom in the first five system, whereas, in the other five system substituted made by bromine atoms. These teen systems are studied by means of computational quantum method-DFT at MPWB95/6-311+G(d,p) level of theory. The results show that the 3-bromo-8-methoxypsoralen (X5 system; of bromine substituted case) has the smallest transition state energy among all suggested teen compounds with a barrier accounted only 2.92 kcal/mol. Optimization of the neutral, radical anion and radcial cation, triplet state, electron affinity, ionization potential, transition state energy, defluorination or debromination process of each system is obtained and discussed in detail.   Â
References
[1] Chilin, A.; Marzano, C.; Guiotto, A.; Manzini, P.; Baccichetti, F.; Carlassare, F. and Bordin, F., Synthesis and biological activity of (hydroxymethyl)- and (diethylaminomethyl) benzopsoralens., J. Med. Chem. 1999, 42, 2936-2945.
[2] Mobilio, S.; Tondelli, L.; Capobianco, M.; and Gia, O., Sequence specificity of tetrahydrobenzopsoralen photobinding to DNA, J. Photochem. Photobiol. 1995, 61, 113-117.
[3] Gia, O.; Mobilio, S.; Palumbo, M.; and Pathak, M. A., Benzo- and tetrahydrobenzo-psoralen congeners: DNA binding and photobiological properties, J. Photochem. Photobiol. 1993, 57, 497-503.
[4] Bordin, F.; Dallacqua, F.; and Guiotto, A., Angelicins, angular analogues of psoralens chemistry, photochemical photobiological and photochemotherapeutic properties. Pharmacol. Ther. 1991, 52, 331-363.
[5] Leite, V. C.; Santos, R. F.; Chen, L. C.; and Guillo, L. A., Psoralen derivatives and longwave ultraviolet irradiation are active in vitro against human melanoma cell line, J. Photochem. Photobiol. B-Biol. 2004, 76, 49-53.
[6] Jarvenpaa, E. P.; Jestoi, M. N.; and Huopalahti, R., Quantitative determination of phototoxic furocoumarins in celeriac (Apium graveolens L. var. rapeceum) using supercritical fluid extraction and high performance liquid chromatography, Phytochem. Anal. 1997, 8, 250-256.
[7] Bettero, A.; and Benassi, C. A., Determination of bergapten and citropten in perfumes and suntan cosmetics by high-performance liquid chromatography and fluorescence, Journal of Chromatography 1983, 280, 167-171.
[8] Chimichi, S.; Boccalini, M.; Cosimelli, B.; Viola, G.; Vedaldi, D.; and Dallacqua, F., A convenient synthesis of psoralens, Tetrahedron 2002, 58, 4859-4863.
[9] Nigg, H. N.; Strandberg, J. O.; Beier, R. C.; Petersen, H. D.; and Harrison, J. M., Furanocoumarins in Florida celery varieties increased by fungicide treatment, J. Agric. Food Chem. 1997, 45, 1430-1436.
[10] Kreimer-Erlacher, H.; Seidl, H.; Back, B.; Cerroni, L.; Kerl, H.; and Wolf, P., High Frequency of Ultraviolet Mutations at the INK4a-ARF Locus in Squamous Cell Carcinomas from Psoralen-Plus-Ultraviolet-A-Treated Psoriasis Patients, J. Invest. Dermatol. 2003, 120, 676-682.
[11] Vilegas, J. H. Y.; Lancas, F. M.; Vilegas, W.; and Pozetti, G. L., Further triterpenes, steroids and furocoumarins from brazilian medicinal plants of dorstenia genus (moraceae), J. Braz. Chem. Soc. 1997, 8, 529-535.
[12] Franke, K.; Porzel, A.; Masaoud, M.; Adam, G.; and Schmidt, J., Furanocoumarins from Dorstenia gigas, Phytochemistry 2001, 56, 611-621.
[13] Dercks, W.; Trumble, J.; and Winter, C., Impact of atmospheric pollution on linear furanocoumarin content in celery, J. Chem. Ecol. 1990, 16, 443-454.
[14] Isaacs, S. T.; Shen, C. J.; Hearst, J. E.; and Rapoport, H., Synthesis and characterization of new psoralen derivatives with superior photoreactivity with DNA and RNA, Biochemistry 1977, 16, 1058-1064.
[15] Furlong, T.; Leisenring, W.; Storb, R.; Anasetti, C.; Appelbaum, F. R.; Carpenter, P. A.; Deeg, H. J.; Doney, K.; Kiem, H. P.; Nash, R. A.; Sanders, J. E.; Witherspoon, R.; Thompson, D.; and Martin, P. Psoralen and ultraviolet A irradiation (PUVA) as therapy for steroid-resistant cutaneous acute graft-versus-host disease, J. Biol. Blood Marrow Transplant. 2002, 8, 206-212.
[16] Gasparro, F. P.; Liao, B.; Foley, P. J.; Wang, X. M.; and McNiff, J. M., Psoralen Photochemotherapy, Clinical Efficacy, and Photomutagenicity: The Role of Molecular Epidemiology in Minimizing Risks, Environ. Mol. Mutagen. 1998, 31, 105-112.
[17] Omar, A.; Wiesmann, U. N.; and Krebs, A., Polyploidization and hemiploidization induced by PUVA in vivo, Dermatologica 1979, 159, 195-209.
[18] Oliven, A.; and Shechter, Y., Extracorporeal photopheresis: a review, Blood Rev. 2001, 15, 103-108.
[19] Klosner, G.; Trautinger, F.; Knobler, R.; and Neuner, P., Treatment of Peripheral Blood Mononuclear Cells with 8-Methoxypsoralen plus Ultraviolet A Radiation Induces a Shift in Cytokine Expression from a Th1 to a Th2 Response, J. Invest. Dermatol. 2001, 116, 459-462.
[20] Steen, V. D.; and Medsger, T. A., Improvement in skin thickening in systemic sclerosis associated with improved survival, Arthritis Rheum. 2001, 44, 2828-2835.
[21] Stern, R. S.; Nichols, K. T.; and Vakeva, L. H., Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study, N. Engl. J. Med. 1997, 336, 1041-1045.
[22] Maier, H.; Schemper, M.; Ortel, B.; Binder, M.; Tanew, A.; and Honigsmann, H., Skin Tumors in Photochemotherapy for Psoriasis: A Single-Center Follow-Up of 496 Patients, Dermatology 1996, 193, 185-191.
[23] Lindelof, B.; Sigurgeirsson, B.; Tegner, E.; Larko, O.; Johannesson, A.; Berne, B.; Ljunggren, B.; Andersson, T.; Molin, L.; Nylander-Lundqvist, E.; and Emtestam, L., PUVA and cancer risk: the Swedish follow-up study, Br. J. Dermatol. 1999, 141, 108-112.
[24] Luftl, M.; Degitz, K.; Plewig, G.; and Rocken, M., Psoralen Bath Plus UV-A Therapy Possibilities and Limitations, Arch. Dermatol. 1997, 133, 1597-1603.
[25] Derie, M. A.; Vaneendenburg, J. P.; Versnick, A. C.; Stolk, L. M. L.; Bos, J. D.; and Westerhof, W., A new psoralen-containing gel for topical PUVA therapy: development, and treatment results in patients with palmoplantar and plaque-type psoriasis, and hyperkeratotic eczema, Br. J. Dermatol. 1995, 132, 964-969.
[26] Grundmann-Kollmann, M.; Behrens, S.; Peter, R. U.; and Kerscher, M., Treatment of severe recalcitrant dermatoses of the palms and soles with PUVA-bath versus PUVA-cream therapy, Photodermatol. Photoimmunol. Photomed. 1999, 15, 87-89.
[27] Grundmann-Kollmann, M.; Ochsendorf, F.; Zollner, T. M.; Spieth, K.; Kaufmann R.; and Podda, M., Cream PUVA therapy for scleredema adultorum, Br. J. Dermatol. 2000, 142, 1058-1059.
[28] Von Kobyletzki, G.; Hoffmann, K.; Kerscher, M.; and Altmeyer, P., Plasma levels G. von Kobyletzki, K. Hoffmann, of 8-methoxypsoralen following PUVA-bath photochemotherapy, Photodermatol. Photoimmunol. Photomed. 1998, 14, 136-138.
[29] Thomas, S. E.; Osullivan, J.; and Balac, N., Plasma levels of 8-methoxypsoralen following oral or bath-water treatment, Br. J. Dermatol. 1991, 125, 56-58.
[30] Becke, A. D., Density-functional thermochemistry. IV. A new dynamical correlation functional and implications for exact-exchange mixing, J. Chem. Phys. 1996, 104, 1040-1046.
[31] Cances, E.; Mennucci, B.; Tomasi, J., A new integral equation formalism for the polarizable continuum model: Theoretical background and applications to isotropic and anisotropic dielectrics. Journal of Chemical Physics 1997, 107, (8), 3032-3041.
[32] Mennucci, B.; Tomasi, J., Continuum solvation models: A new approach to the problem of solute's charge distribution and cavity boundaries. Journal of Chemical Physics 1997, 106, (12), 5151-5158.
[33] Cossi, M.; Scalmani, G.; Rega, N.; and Barone, V., New developments in the polarizable continuum model for quantum mechanical and classicalcalculations on molecules in solution. J. Chem. Phys. 2002, 117, (1), 43-54.
[34] Gaussian 03, R. B., Frisch, M. J.;Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian, Inc., Wallingford CT, 2004.
[35] Lissi, E. A.; Encinas, M. V.; Lemp, E.; Rubio, M. A., Singlet oxygen O2(Δg) bimolecular processes – solvent and comparatmentalization effects. Chemical Reviews 1993, 93, 699-723.
[2] Mobilio, S.; Tondelli, L.; Capobianco, M.; and Gia, O., Sequence specificity of tetrahydrobenzopsoralen photobinding to DNA, J. Photochem. Photobiol. 1995, 61, 113-117.
[3] Gia, O.; Mobilio, S.; Palumbo, M.; and Pathak, M. A., Benzo- and tetrahydrobenzo-psoralen congeners: DNA binding and photobiological properties, J. Photochem. Photobiol. 1993, 57, 497-503.
[4] Bordin, F.; Dallacqua, F.; and Guiotto, A., Angelicins, angular analogues of psoralens chemistry, photochemical photobiological and photochemotherapeutic properties. Pharmacol. Ther. 1991, 52, 331-363.
[5] Leite, V. C.; Santos, R. F.; Chen, L. C.; and Guillo, L. A., Psoralen derivatives and longwave ultraviolet irradiation are active in vitro against human melanoma cell line, J. Photochem. Photobiol. B-Biol. 2004, 76, 49-53.
[6] Jarvenpaa, E. P.; Jestoi, M. N.; and Huopalahti, R., Quantitative determination of phototoxic furocoumarins in celeriac (Apium graveolens L. var. rapeceum) using supercritical fluid extraction and high performance liquid chromatography, Phytochem. Anal. 1997, 8, 250-256.
[7] Bettero, A.; and Benassi, C. A., Determination of bergapten and citropten in perfumes and suntan cosmetics by high-performance liquid chromatography and fluorescence, Journal of Chromatography 1983, 280, 167-171.
[8] Chimichi, S.; Boccalini, M.; Cosimelli, B.; Viola, G.; Vedaldi, D.; and Dallacqua, F., A convenient synthesis of psoralens, Tetrahedron 2002, 58, 4859-4863.
[9] Nigg, H. N.; Strandberg, J. O.; Beier, R. C.; Petersen, H. D.; and Harrison, J. M., Furanocoumarins in Florida celery varieties increased by fungicide treatment, J. Agric. Food Chem. 1997, 45, 1430-1436.
[10] Kreimer-Erlacher, H.; Seidl, H.; Back, B.; Cerroni, L.; Kerl, H.; and Wolf, P., High Frequency of Ultraviolet Mutations at the INK4a-ARF Locus in Squamous Cell Carcinomas from Psoralen-Plus-Ultraviolet-A-Treated Psoriasis Patients, J. Invest. Dermatol. 2003, 120, 676-682.
[11] Vilegas, J. H. Y.; Lancas, F. M.; Vilegas, W.; and Pozetti, G. L., Further triterpenes, steroids and furocoumarins from brazilian medicinal plants of dorstenia genus (moraceae), J. Braz. Chem. Soc. 1997, 8, 529-535.
[12] Franke, K.; Porzel, A.; Masaoud, M.; Adam, G.; and Schmidt, J., Furanocoumarins from Dorstenia gigas, Phytochemistry 2001, 56, 611-621.
[13] Dercks, W.; Trumble, J.; and Winter, C., Impact of atmospheric pollution on linear furanocoumarin content in celery, J. Chem. Ecol. 1990, 16, 443-454.
[14] Isaacs, S. T.; Shen, C. J.; Hearst, J. E.; and Rapoport, H., Synthesis and characterization of new psoralen derivatives with superior photoreactivity with DNA and RNA, Biochemistry 1977, 16, 1058-1064.
[15] Furlong, T.; Leisenring, W.; Storb, R.; Anasetti, C.; Appelbaum, F. R.; Carpenter, P. A.; Deeg, H. J.; Doney, K.; Kiem, H. P.; Nash, R. A.; Sanders, J. E.; Witherspoon, R.; Thompson, D.; and Martin, P. Psoralen and ultraviolet A irradiation (PUVA) as therapy for steroid-resistant cutaneous acute graft-versus-host disease, J. Biol. Blood Marrow Transplant. 2002, 8, 206-212.
[16] Gasparro, F. P.; Liao, B.; Foley, P. J.; Wang, X. M.; and McNiff, J. M., Psoralen Photochemotherapy, Clinical Efficacy, and Photomutagenicity: The Role of Molecular Epidemiology in Minimizing Risks, Environ. Mol. Mutagen. 1998, 31, 105-112.
[17] Omar, A.; Wiesmann, U. N.; and Krebs, A., Polyploidization and hemiploidization induced by PUVA in vivo, Dermatologica 1979, 159, 195-209.
[18] Oliven, A.; and Shechter, Y., Extracorporeal photopheresis: a review, Blood Rev. 2001, 15, 103-108.
[19] Klosner, G.; Trautinger, F.; Knobler, R.; and Neuner, P., Treatment of Peripheral Blood Mononuclear Cells with 8-Methoxypsoralen plus Ultraviolet A Radiation Induces a Shift in Cytokine Expression from a Th1 to a Th2 Response, J. Invest. Dermatol. 2001, 116, 459-462.
[20] Steen, V. D.; and Medsger, T. A., Improvement in skin thickening in systemic sclerosis associated with improved survival, Arthritis Rheum. 2001, 44, 2828-2835.
[21] Stern, R. S.; Nichols, K. T.; and Vakeva, L. H., Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study, N. Engl. J. Med. 1997, 336, 1041-1045.
[22] Maier, H.; Schemper, M.; Ortel, B.; Binder, M.; Tanew, A.; and Honigsmann, H., Skin Tumors in Photochemotherapy for Psoriasis: A Single-Center Follow-Up of 496 Patients, Dermatology 1996, 193, 185-191.
[23] Lindelof, B.; Sigurgeirsson, B.; Tegner, E.; Larko, O.; Johannesson, A.; Berne, B.; Ljunggren, B.; Andersson, T.; Molin, L.; Nylander-Lundqvist, E.; and Emtestam, L., PUVA and cancer risk: the Swedish follow-up study, Br. J. Dermatol. 1999, 141, 108-112.
[24] Luftl, M.; Degitz, K.; Plewig, G.; and Rocken, M., Psoralen Bath Plus UV-A Therapy Possibilities and Limitations, Arch. Dermatol. 1997, 133, 1597-1603.
[25] Derie, M. A.; Vaneendenburg, J. P.; Versnick, A. C.; Stolk, L. M. L.; Bos, J. D.; and Westerhof, W., A new psoralen-containing gel for topical PUVA therapy: development, and treatment results in patients with palmoplantar and plaque-type psoriasis, and hyperkeratotic eczema, Br. J. Dermatol. 1995, 132, 964-969.
[26] Grundmann-Kollmann, M.; Behrens, S.; Peter, R. U.; and Kerscher, M., Treatment of severe recalcitrant dermatoses of the palms and soles with PUVA-bath versus PUVA-cream therapy, Photodermatol. Photoimmunol. Photomed. 1999, 15, 87-89.
[27] Grundmann-Kollmann, M.; Ochsendorf, F.; Zollner, T. M.; Spieth, K.; Kaufmann R.; and Podda, M., Cream PUVA therapy for scleredema adultorum, Br. J. Dermatol. 2000, 142, 1058-1059.
[28] Von Kobyletzki, G.; Hoffmann, K.; Kerscher, M.; and Altmeyer, P., Plasma levels G. von Kobyletzki, K. Hoffmann, of 8-methoxypsoralen following PUVA-bath photochemotherapy, Photodermatol. Photoimmunol. Photomed. 1998, 14, 136-138.
[29] Thomas, S. E.; Osullivan, J.; and Balac, N., Plasma levels of 8-methoxypsoralen following oral or bath-water treatment, Br. J. Dermatol. 1991, 125, 56-58.
[30] Becke, A. D., Density-functional thermochemistry. IV. A new dynamical correlation functional and implications for exact-exchange mixing, J. Chem. Phys. 1996, 104, 1040-1046.
[31] Cances, E.; Mennucci, B.; Tomasi, J., A new integral equation formalism for the polarizable continuum model: Theoretical background and applications to isotropic and anisotropic dielectrics. Journal of Chemical Physics 1997, 107, (8), 3032-3041.
[32] Mennucci, B.; Tomasi, J., Continuum solvation models: A new approach to the problem of solute's charge distribution and cavity boundaries. Journal of Chemical Physics 1997, 106, (12), 5151-5158.
[33] Cossi, M.; Scalmani, G.; Rega, N.; and Barone, V., New developments in the polarizable continuum model for quantum mechanical and classicalcalculations on molecules in solution. J. Chem. Phys. 2002, 117, (1), 43-54.
[34] Gaussian 03, R. B., Frisch, M. J.;Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian, Inc., Wallingford CT, 2004.
[35] Lissi, E. A.; Encinas, M. V.; Lemp, E.; Rubio, M. A., Singlet oxygen O2(Δg) bimolecular processes – solvent and comparatmentalization effects. Chemical Reviews 1993, 93, 699-723.
Additional Files
Published
2018-10-14
How to Cite
Photo-stability and Photo-reactivity of halogenated 8-methoxypsoralen, the basis for designing of new drugs. (2018). Lebda Medical Journal, 5(1), 180–185. Retrieved from https://lebmedj.elmergib.edu.ly/index.php/LMJ/article/view/89
Issue
Section
Pharmacy
