A Theoretical Study on the Stability, Reactivity and Protonic Affinity of 2-Phenylbenzothiazole Derivatives
The 2-phenylbenzothiazole derivatives have antitumor activities. Work has shown that these derivatives have mesomeric forms. The electrophilic centers of these mesomers form adducts with the nucleophilic centers of deoxyribonucleic acid (DNA). These adducts destroy the tumor cells and prevent the proliferation of these. In this sense, the knowledge of electrophilic sites, nucleophiles and the capacity to protonate these derivatives is therefore useful if we want to know their future in the biological environment. Using DFT/B3LYP method associated with the bases 6-31G (d, p) and 6-31+G (d, p), this work aims at determining the preferential protonation site, the electrophilic and nucleophilic centers of six 2-phenylbenzothiazole. This study also analyzes the stability of these derivatives. Calculations are carried out in gas and aqueous phases. Results show that fluorinated derivatives are the most stable. 2-(4-aminophenyl) benzothiazoles are the most reactive. The atoms carbon C4, C5 and C6 of benzothiazole ring are the most electrophilic. Interactions of these derivatives with nucleophilic centers of deoxyribonucleic acid (DNA) will probably be at these atoms. Nitrogen sp2 (N1) of benzothiazole ring remains the most nucleophilic center and the preferential site of protonation in all the molecules studied. These results highlight the influence of the substituents on the basicity of the nitrogen sp2 (N1) and reactivity of the 2-phenylbenzothiazole derivatives studied.
Bede Affoue Lucie,
N’Guessan Boka Robert,
Yapo Kicho Denis,
A Theoretical Study on the Stability, Reactivity and Protonic Affinity of 2-Phenylbenzothiazole Derivatives, Modern Chemistry. Special Issue: Advanced Journal of Chemistry.
Vol. 7, No. 3,
2019, pp. 65-72.
A. Ly, Current issues and future prospects in cancer prevention in developing countries, African Journal of Cancer, 2011, 3, 4, 268‑272.
J. M. Dangou, B.-H. Sambo, M. Moeti and A.-J. Diarra-Nama, Prévention et lutte contre le cancer dans la région africaine de l’OMS: un appel à l’action, African Journal of Cancer, 2009, 1, 1, 56‑60.
D. Moukassa, A. M. Boumba, C. F. Ngatali, A. Ebatetou, J. B. N. Mbon and J.-R. Ibara, Virus-Induced Cancers in Africa: Epidemiology and Carcinogenesis Mechanisms, Open Journal of Pathology, 2018, 8, 1-14.
M. Ly, A. Ly, M. Rodrigues, Y. Loriot, M. Deberne, PP. Boudou-Rouquette, T. Bathily and D. Diallo, Cancer in Africa, a new health challenge. Examples of Mali and OncoMali, Bulletin du Cancer, 2010, 97, 8, 965‑968.
H. B. El–Serag, and K. L. Rudolph, Hepatocellular Carcinoma: Epidemiology and Molecular Carcinogenesis, Gastroenterology, 2007, 132, 7, 2557–2576.
X. Peng, G. Xie, Z. Wang, H. Lin, T. Zhou, P. Xiang and Y. Zhao, SKLB-163, a new benzothiazole-2-thiol derivative, exhibits potent anticancer activity by affecting RhoGDI/JNK-1 signaling pathway, Cell Death & Disease, 2014, 5, 3, e1143.
S. Ke, Y. Wei, Z. Yang, K. Wang, Y. Liang and L. Shi, Novel cycloalkylthiophene–imine derivatives bearing benzothiazole scaffold: Synthesis, characterization and antiviral activity evaluation, Bioorganic & Medicinal Chemistry Letters, 2013, 23, 18, 5131‑5134.
J. Zhang, Z. Q. Cheng, J. L. Song, H. R. Tao, K. Zhu, L. A. Muehlmann, C. S. Jiang and H. Zhang, Synthesis and biological evaluation of 2-(3-aminophenyl)-benzothiazoles as antiproliferative and apoptosis-inducing agents, Monatshefte Für Chemie-Chemical Monthly, 2018, 149, 11, 2093‑2102.
P. Linciano, C. Pozzi, L. D. Iacono, F. di PIsa, G. Landi, A. Bonucci, S. Gul, M. Kuzikov, B. Ellinger, G. Witt, N. Santarem, C. Baptista, C. Franco, C. B. Moraes, W. Müller, U. Wittig, R. Luciani, A. Sesenna, A. Quotadamo, S. Ferrari, I. Pöhner, A. C. Da-Silva, S. Mangani, L. Costantino, and M. P. Costi, Enhancement of Benzothiazoles as Pteridine Reductase-1 Inhibitors for the Treatment of Trypanosomatidic Infections, Journal of Medicinal Chemistry, 2019, 62, 8, 3989‑4012.
A. Trapania, A. Catalanoa, A. Caroccia, A. Carrieria, A. Mercurioa, A. Rosatoa, D. Mandracchiaa, G. Tripodob, B. I. P. Schiavonea, C. Franchinia, E. Mestoc, E. Schingaroc and F. Corboa, Effect of Methyl-β-Cyclodextrin on the antimicrobial activity of a new series of poorly water-soluble benzothiazoles, Carbohydrate Polymers, 2019, 207, 720‑728.
J. A. Johnson, G. Tora, Z. Pi, M. Phillips, X. Yin, R. Yang, L. Zhao, A. Y. Chen, D. S. Taylor, M. Basso, A. Rose, K. Behnia, J. Onorato, X. Q. Chen, L. M. Abell, H. Lu, G. Locke, C. Caporuscio, M. Galella, L. P. Adam, D. Gordon, R. R. Wexler and H. J. Finlay, Sulfonylated Benzothiazoles as Inhibitors of Endothelial Lipase, ACS Medicinal Chemistry Letters, 2018, 9, 12, 1263‑1268.
M. N. Noolvi, H. M. Patel, and M. Kaur, Benzothiazoles: search for anticancer agents, European journal of medicinal chemistry, 2012, 54, 447‑462.
C. G. Mortimer, G. Wells, J. P. Crochard, E. L. Stone, T. D. Bradshaw, M. F. G. Stevens and A. D. Westwell, Antitumor Benzothiazoles. 26. 2-(3, 4-Dimethoxyphenyl) -5-fluorobenzothiazole (GW 610, NSC 721648), a Simple Fluorinated 2-Arylbenzothiazole, Shows Potent and Selective Inhibitory Activity against Lung, Colon, and Breast Cancer Cell Lines, Journal of Medicinal Chemistry, 2006, 49, 1, 179‑185.
T. D. Bradshaw and A. D. Westwell, The development of the antitumour benzothiazole prodrug, Phortress, as a clinical candidate, Current medicinal chemistry, 2004, 11, 8, 1009-1021.
I. Hutchinson, M. S. Chua, H. L. Browne, V. Trapani, T. D. Bradshaw, A. D. Westwell and M. F. G. Stevens, Antitumor Benzothiazoles. 14.1 Synthesis and in Vitro Biological Properties of Fluorinated 2- (4-Aminophenyl) benzothiazoles, Journal of Medicinal Chemistry, 2001, 44, 9, 1446‑1455.
E. Brantley, V. Patel, S. F. Stinson, V. Trapani, C. D. Hose, H. P. Ciolino, G. C. Yeh, J. S. Gutkind, E. A. Sausville and A. I. Loaiza-Pérez, The antitumor drug candidate 2-(4-amino-3-methylphenyl) -5-fluorobenzothiazole induces NF-κB activity in drug-sensitive MCF-7 cells, AntiCancer Drugs, 2005, 16, 2, 137-142.
S. H. Kok, R. Gambari, C. H. Chui, M. C. Yuen, E. Lin, R. S. Wong, F. Y. Lau, G. Y. Cheng, W. S. Lam, S. H. Chan, K. H. Lam, C. H. Cheng, P. B. Lai, M. W. Yu, F. Cheung, J. C. Tang and A. S. C. Chan, Synthesis and anticancer activity of benzothiazole containing phthalimide on human carcinoma cell lines, Bioorganic & Medicinal Chemistry, 2008, 16, 7, 3626‑3631.
Y. Zhang, M. Chakraborty, C. G. Cerda-Smith, R. N. Bratton, N. E. Maurer, E. M. Senser, and M. Novak., Chemistry of Ring-Substituted 4- (Benzothiazol-2-yl) phenylnitrenium Ions from Antitumor 2- (4-Aminophenyl) benzothiazoles. Journal of Organic Chemistry, 2013, 78, 14, 6992‑7000.
T. D. Bradshaw, D. F. Shi, R. J. Schultz, K. D. Paull, L. Kelland, A. Wilson, C. Garner, H. H. Fiebig, S. Wrigley and M. F. G. Stevens, Influence of 2-(4-aminophenyl) benzothiazoles on growth of human ovarian carcinoma cells in vitro and in vivo, British Journal of Cancer, 1998, 78, 4, 421-429.
A. Wallqvist, J. Connelly, E. A. Sausville, D. G. Covell, and A. Monks, Differential Gene Expression as a potential classifier of 5F-203 Sensitive and Insensitive Cell Lines, Molecular Pharmacology, 2006, 69, 3, 737‑748.
S. Aiello, G. Wells, E. L. Stone, H. Kadri, R. Bazzi, D. R. Bell, M. F. G. Stevens, C. S. Matthews, T. D. Bradshaw and A. D. Westwell, Synthesis and Biological Properties of Benzothiazole, Benzoxazole, and Chromen-4-one Analogues of the Potent Antitumor Agent 2-(3, 4-Dimethoxyphenyl) -5-fluorobenzothiazole (PMX 610, NSC 721648) (1). Journal of Medicinal Chemistry, 2008, 51, 16, 5135‑5139.
C. O. Leong, M. Suggitt, D. J. Swaine, M. C. Bibby, M. F. G. Stevens, and T. D. Bradshaw, In vitro, in vivo, and in silico analyses of the antitumor activity of 2-(4-amino-3-methylphenyl) -5-fluorobenzothiazoles, Molecular Cancer Therapeutics, 2004, 3, 12, 1565‑1575.
T. D. Bradshaw, E. L. Stone, V. Trapani, C. O. Leong, C. S. Matthews, R. Poele, M. F. G. Stevens, Mechanisms of acquired resistance to 2-(4-Amino-3-methylphenyl) benzothiazole in breast cancer cell lines, Breast Cancer Research and Treatment, 2008, 110, 1, 57‑68.
M. S. Chua, E. Kashiyama, T. D. Bradshaw, S. F. Stinson, E. Brantley, E. A. Sausville, and M. F. Stevens, Role of CYP1A1 in Modulation of Antitumor Properties of the Novel Agent 2- (4-Amino-3-methylphenyl) benzothiazole (DF 203, NSC 674495) in Human Breast Cancer Cells, Cancer Research, 2000, 60, 5196-5203.
B. S. Tan, K. H. Tiong, A. Muruhadas, N. Randhawa, H. L. Choo, T. D. Bradshaw, M. F. G. Stevens and C. O. Leong, CYP2S1 and CYP2W1 mediate 2-(3, 4-dimethoxyphenyl)-5-fluorobenzothiazole (GW-610, NSC 721648) sensitivity in breast and colorectal cancer cells, Molecular Cancer Therapeutics, 2011, 10, 1982‑1992.
A. D. Becke, Density-functional thermochemistry. V. Systematic optimization of exchange-correlation functionals, Journal of chemical physics, 1997, 107, 20, 8554‑8560.
R. Bauernschmitt and R. Ahlrichs, Stability analysis for solutions of the closed shell Kohn–Sham equation, Journal of chemical physics, 1996, 104, 22, 9047‑9052.
C. Lee, W. Yang, and R. G. Parr, Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density, Physical review B, 1988, 37, 2, 785‑789.
A. D. Becke, Density‐functional thermochemistry. I. The effect of the exchange‐only gradient correction, Journal of chemical physics, 1993, 98, 7, 5648‑5652.
M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E., Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr., T. Vreven, K., N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B., Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M., Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J., B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K., Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S., Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D., Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I., Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A., Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W., Wong, C. Gonzalez, et J. A. Pople, Gaussian, Inc., Pittsburgh PA. Gaussian 03, Revision A.1, 2003.
E. Cancès, B. Mennucci, and J. Tomasi, 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.
G. E. Scuseria, T. J. Lee, R. J. Saykally, and H. F. Schaefer, Nitrogen quadrupole coupling constants for HCN and H2CN+: Explanation of the absence of fine structure in the microwave spectrum of interstellar H2CN+, Journal of chemical, 1986, 84, 10, 5711‑5714.
M. C. Rezende, A theoretical HSAB study of the acidity of carbon acids CH3Z, Journal of the Brazilian Chemical Society, 2001, 12, 1, 73‑80.
C. Møller and M. S. Plesset, Note on an approximation treatment for many-electron systems, Physical review, 1934, 46, 7, 618‑622.
R. G. Parr, R. A. Donnelly, M. Levy, and W. E. Palke, Electronegativity: The density functional viewpoint, Journal of Chemical Physics, 1978, 68, 8, 3801‑3807.
C. Morell, A. Grand, and A. Toro-Labbé, New dual descriptor for chemical reactivity, Journal of Physical Chemistry A, 2005, 109, 1, 205‑212.
P. Bultinck, D. Clarisse, PP. W. Ayers, and R. Carbo-Dorca, The Fukui matrix: a simple approach to the analysis of the Fukui function and its positive character, Physical Chemistry Chemical Physics, 2011, 13, 6110‑6115.
J. Melin, PP. W. Ayers, and J. V. Ortiz, Removing electrons can increase the electron density: a computational study of negative Fukui functions, Journal of Physical Chemistry A, 2007, 111, 40, 10017‑10019.
H. Eljazouli, H. Kabli, T. Atbir, M. Elamine, and A. Albourine, Protonation of Uracil, Thymin and 5-Halogénouracil Examined at the Isolated State. Calculation of the Protonic Affinitys by the AM1 Method, Physical & Chemical News, 2007, 34, 97-104.
M. D. Liptak, K. C. Gross, PP. G. Seybold, S. Feldgus, and G. C. Shields, Absolute pKa Determinations for Substituted Phenols, Journal of the American Chemical Society, 2002, 124, 22, 6421‑6427.
B. R. Scott, G. L. Dorn, E. Käfer, and R. Stafford, Aspergillus nidulans: systems and results of tests for induction of mitotic segregation and mutation. II. Haploid assay systems and overall response of all systems. A report of the U.S. EPA Gene-Tox Program, Mutation Research, 1982, 98, 1, 49‑94.
M. Belletête, J.-F. Morin, M. Leclerc, and G. Durocher, A Theoretical, Spectroscopic, and Photophysical Study of 2, 7-Carbazolenevinylene-Based Conjugated Derivatives, Journal of Physical Chemistry A, 2005, 109, 31, 6953‑6959.
J. Aihara, Reduced HOMO−LUMO gap as an index of kinetic stability for polycyclic aromatic hydrocarbons, Journal of Physical Chemistry A, 1999, 103, 37, 7487‑7495.
A. A. Shabana, I. S. Butler, D. F. R. Gilson, B. J. Jean-Claude, Z. S. Mouhri, M. M. Mostafa, and S. I. Mostafa, Synthesis, characterization, anticancer activity and DNA interaction studies of new 2-aminobenzothiazole complexes; crystal structure and DFT calculations of [Ag(Habt)2] ClO4, Inorganica Chimica Acta, 2014, 423, 242‑255.
C. O. Leong, M. Gaskell, E. A. Martin, R. T. Heydon, P. B. Farmer, M. C. Bibby, P. A. Cooper, J. A. Double, T. D. Bradshaw and M. F. G. Stevens, Antitumour 2-(4aminophenyl) benzothiazoles generate DNA adducts in sensitive tumour cells in vitro and in vivo, British Journal of Cancer, 2003, 88, 3, 470-477.
R. K. Roy, S. Pal, and K. Hirao, On non-negativity of Fukui function indices, Journal of chemical physics, 1999, 110, 17, 8236‑8245.