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Noboru Motohashi - One of the best experts on this subject based on the ideXlab platform.
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Antitumor Potential and Possible Targets of Phenothiazine-Related Compounds
Current drug targets, 2000Co-Authors: Noboru Motohashi, Masami Kawase, Setsuo Saito, Hiroshi SakagamiAbstract:Phenothiazines and its related compounds have shown diverse biological activities including psychotropic, anticancer and other pharmacological activities. Recent studies have suggested the possible interactions between Phenothiazines and their physiological targets or potential receptors. New types of Phenothiazine, such as "half-mustard type" Phenothiazines and benzo[a]Phenothiazines, have been synthesized. These compounds stimulated T-cell blast formation, natural killer cell activity (possibly via activation of monocytes and macrophages) and antibody-dependent cellular cytotoxicity of human peripheral blood mononuclear cells, and showed cytotoxicity against several human cancer cell lines. Benzo[a]Phenothiazines induced monocytic differentiation and apoptotic cell death (characterized by internucleosomal DNA fragmentation) in human myelogenous leukemic cell lines, but not in other cancer cell lines. These compounds also induced antimicrobial activity in vivo, possibly by host-mediated immunopotentiation. On the other hand, Phenothiazines did not induce such immunopotentiation activity, but showed direct antibacterial activity in vitro. There was positive relation between their radical intensity and biological activities. These compounds did not show any apparent mutagenic activity, but rather be antimutagenic. These data suggest their possible applicability of "half-mustard type" Phenothiazines and benzo[a]Phenothiazines for cancer chemotherapy.
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A solvatochromic study of new benzo[a]Phenothiazines for the determination of dipole moments and specific solute—solvent interactions in the first excited singlet state
Journal of Photochemistry and Photobiology A: Chemistry, 1996Co-Authors: Jean-jacques Aaron, Cyril Párkányi, Maged Shafik Antonious, Mounir Maafi, Christophe Kersebet, Noboru MotohashiAbstract:Abstract The electronic absorption and fluorescence excitation and emission spectra of seven benzo[a]Phenothiazines, including 12H-benzo[a]Phenothiazine, 9-methyl-benzo[a]Phenothiazine, 10-methyl-benzo[a]Phenothiazine, 11-methyl-benzo[a]Phenothiazine, 5-oxo-5H-benzo[a]Phenothiazine, 5-oxo-6-methyl-benzo[a]Phenothiazine and 5-oxo-6-hydroxy-benzo[a]Phenothiazine, were determined at room temperature (298 K) in solvents of various polarity (cyclohexane, ethyl ether, ethyl acetate, tetrahydrofuran, ethanol, dimethylformamide, acetonitrile and dimethylsulphoxide). The effect of the solvent on the spectral characteristics was studied quantitatively. In combination with the ground state dipole moments of these compounds, the spectral data of the benzo[a]Phenothiazines were used to evaluate their first excited singlet state dipole moments using the solvatochromic shift method (Bakhshiev and Kawski—Chamma—Viallet correlations). The theoretical ground and excited singlet state dipole moments of the benzo[a]Phenothiazines were also calculated as the vector sum of the π component (obtained by the Pariser—Parr—Pople method) and the σ component (obtained from σ bond moments). In most cases, a satisfactory agreement was found between the experimental and calculated values of the dipole moments. For most benzo[a]Phenothiazine derivatives under study, the experimental excited singlet state dipole moments were higher than their ground state counterparts. The application of the Kamlet—Abboud—Taft solvatochromic parameters to explain the effect of the solvent on the spectral properties of benzo[a]Phenothiazines is discussed.
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Antiplasmid activity of Phenothiazines, benzo[a]Phenothiazines and benz[c]acridines.
Anticancer research, 1992Co-Authors: Noboru Motohashi, T Kurihara, Hiroshi Sakagami, K CsuriAbstract:Various synthetic derivatives of Phenothiazines, benzo[a]Phenothiazines and benz[c]acridines were compared for their abilities to induce antiplasmid activity against E. coli F'lac plasmid. Several Phenothiazine derivatives were much more potent in antiplasmid activity than benzo[a]Phenothiazine- or benz[c]acridine derivatives. Their antiplasmid activity seemed to be enhanced by Cl- or CF3- substitution at 2 C atom, and modified by the side chain length and charge at the L-region of the molecules, as well as by hydrophilicity.
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Antimicrobial activity of Phenothiazines, benzo[a]Phenothiazines and benz[c]acridines
Anticancer Research, 1992Co-Authors: Noboru Motohashi, K Csuri, Lajos Ferenczy, T Kurihara, Hiroshi Sakagami, Jozsef MolnarAbstract:The abilities of 14 Phenothiazines, 8 benzo[a]Phenothiazines and 12 benz[c]acridines to induce an antibacterial effect against Escherichia coli K12 were compared. Several Phenothiazines, which showed antiplasmid activity, displayed the most potent antibacterial activity. All benz[c]acridine derivatives were moderately antibacterial, whereas benzo[a]Phenothiazines were inactive. The active Phenothiazine derivatives had more potent inhibitory activity against fungi, including phytopathogen flamentous, human pathogen filamentous fungi and yeasts, than against gram-positive and -negative becteria
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Antimicrobial activity of Phenothiazines, benzo[a]Phenothiazines and benz[c]acridines.
Anticancer research, 1992Co-Authors: Noboru Motohashi, K Csuri, Lajos Ferenczy, T Kurihara, Hiroshi Sakagami, Jozsef MolnarAbstract:The abilities of 14 Phenothiazines, 8 benzo[a]Phenothiazines and 12 benz[c]acridines to induce an antibacterial effect against Escherichia coli K12 were compared. Several Phenothiazines, which showed antiplasmid activity, displayed the most potent antibacterial activity. All benz[c]acridine derivatives were moderately antibacterial, whereas benzo[a]Phenothiazines were inactive. The active Phenothiazine derivatives had more potent inhibitory activity against fungi, including phytopathogen filamentous, human pathogen filamentous fungi and yeasts, than against gram-positive and -negative bacteria. Taken together with previously reported data, the induction mechanism of antimicrobial and antiplasmid activity by these compounds seems to be different from that of antitumor, differentiation-inducing and carcinogenic activity.
Kristina Viktorsson - One of the best experts on this subject based on the ideXlab platform.
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harnessing the lysosome dependent antitumor activity of Phenothiazines in human small cell lung cancer
Cell Death and Disease, 2017Co-Authors: D Zong, Katarzyna Zielinskachomej, Therese Juntti, Birgitta Mork, Petra Haag, Rolf Lewensohn, Kristina ViktorssonAbstract:Phenothiazines are a family of heterocyclic compounds whose clinical utility includes treatment of psychiatric disorders as well as chemotherapy-induced emesis. Various studies have demonstrated that these compounds possess cytotoxic activities in tumor cell lines of different origin. However, there is considerable confusion regarding the molecular basis of Phenothiazine-induced cell death. Lung cancer (LC) remains one of the most prevalent and deadly malignancies worldwide despite considerable efforts in the development of treatment strategies, especially new targeted therapies. In this work, we evaluated the potential utility of Phenothiazines in human LC. We show that Phenothiazines as single treatment decreased cell viability and induced cell death preferentially in small cell lung carcinoma (SCLC) over non small cell lung carcinoma (NSCLC) cell lines. Sensitivity to Phenothiazines was not correlated with induction of apoptosis but due to Phenothiazine-induced lysosomal dysfunction. Interestingly, the higher susceptibility of SCLC cells to Phenothiazine-induced cell death correlated with an intrinsically lower buffer capacity in response to disruption of lysosomal homeostasis. Importantly, this effect in SCLC occurred despite mutation in p53 and was not influenced by intrinsic sensitivity/resistance toward conventional chemotherapeutic agents. Our data thus uncovered a novel context-dependent activity of Phenothiazines in SCLC and suggest that Phenothiazines could be considered as a treatment regimen of this disease, however, extended cell line analyses as well as in vivo studies are needed to make such conclusion.
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chemosensitization by Phenothiazines in human lung cancer cells impaired resolution of γh2ax and increased oxidative stress elicit apoptosis associated with lysosomal expansion and intense vacuolation
Cell Death and Disease, 2011Co-Authors: D Zong, Petra Haag, Ihor Yakymovych, Rolf Lewensohn, Kristina ViktorssonAbstract:Chemotherapy resistance poses severe limitations on the efficacy of anti-cancer medications. Recently, the notion of using novel combinations of ‘old' drugs for new indications has garnered significant interest. The potential of using Phenothiazines as chemosensitizers has been suggested earlier but so far our understanding of their molecular targets remains scant. The current study was designed to better define Phenothiazine-sensitive cellular processes in relation to chemosensitivity. We found that Phenothiazines shared the ability to delay γH2AX resolution in DNA-damaged human lung cancer cells. Accordingly, cells co-treated with chemotherapy and Phenothiazines underwent protracted cell-cycle arrest followed by checkpoint escape that led to abnormal mitoses, secondary arrest and/or a form of apoptosis associated with increased endogenous oxidative stress and intense vacuolation. We provide evidence implicating lysosomal dysfunction as a key component of cell death in Phenothiazine co-treated cells, which also exhibited more typical hallmarks of apoptosis including the activation of both caspase-dependent and -independent pathways. Finally, we demonstrated that vacuolation in Phenothiazine co-treated cells could be reduced by ROS scavengers or the vacuolar ATPase inhibitor bafilomycin, leading to increased cell viability. Our data highlight the potential benefit of using Phenothiazines as chemosensitizers in tumors that acquire molecular alterations rendering them insensitive to caspase-mediated apoptosis.
Hiroshi Sakagami - One of the best experts on this subject based on the ideXlab platform.
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Antitumor Potential and Possible Targets of Phenothiazine-Related Compounds
Current drug targets, 2000Co-Authors: Noboru Motohashi, Masami Kawase, Setsuo Saito, Hiroshi SakagamiAbstract:Phenothiazines and its related compounds have shown diverse biological activities including psychotropic, anticancer and other pharmacological activities. Recent studies have suggested the possible interactions between Phenothiazines and their physiological targets or potential receptors. New types of Phenothiazine, such as "half-mustard type" Phenothiazines and benzo[a]Phenothiazines, have been synthesized. These compounds stimulated T-cell blast formation, natural killer cell activity (possibly via activation of monocytes and macrophages) and antibody-dependent cellular cytotoxicity of human peripheral blood mononuclear cells, and showed cytotoxicity against several human cancer cell lines. Benzo[a]Phenothiazines induced monocytic differentiation and apoptotic cell death (characterized by internucleosomal DNA fragmentation) in human myelogenous leukemic cell lines, but not in other cancer cell lines. These compounds also induced antimicrobial activity in vivo, possibly by host-mediated immunopotentiation. On the other hand, Phenothiazines did not induce such immunopotentiation activity, but showed direct antibacterial activity in vitro. There was positive relation between their radical intensity and biological activities. These compounds did not show any apparent mutagenic activity, but rather be antimutagenic. These data suggest their possible applicability of "half-mustard type" Phenothiazines and benzo[a]Phenothiazines for cancer chemotherapy.
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Radical intensity and differentiation-inducing activity of benzo [a] Phenothiazines and Phenothiazines
Anticancer Research, 1997Co-Authors: Satoh K, Hiroshi Sakagami, Teruo Kurihara, Motohashi NAbstract:ESR spectroscopy revealed that 12H-benzo [a]Phenothiazine, 9-methyl-12H-benzo[a]Phenothiazine, 10-methyl- 12H-benzo[a]Phenothiazine, 11-methyl-12H-benzo[a]-Phenothiazine and 5-oxo-5H-benzo[a]Phenothiazine, which induced the differentiation of human myelogenous leukemic cell lines into maturing macrophages, produced radical(s) under an alkaline condition. On the other hand, 6-hydroxy-5-oxo-5H-benzo[a]Phenothiazine, 6-methyl-5-oxo-5H-benzo[a]Phenothiazine and 5H-benzo[a][1,4]benwthiazino-[3,2-c]Phenothiazine, and 13 Phenothiazines, which had little or no differentiation-inducing activity, produced no detectable amounts of radical(s). Using Hiickel molecular orbital (HMO) method, these active benzo[a]Phenothiazines were shown to have the elevated n-spin density at the sulfur atom of their molecules. Seven out of 8 benzo[a]Phenothiazines significantly enhanced the radical intensity of sodium L-ascorbate and sodium 5,6-benzylidene-L-ascorbate (SBA), whereas only 3 out of 13 Phenothiazines showed similar effects. These data suggest that the induction of human leukemic cell differentiation by benzo[a]Phenothiazines might be initiated by radical mediated reactions.
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Radical intensity and differentiation-inducing activity of benzo [a] Phenothiazines and Phenothiazines
Anticancer Research, 1997Co-Authors: Satoh K, Hiroshi Sakagami, Teruo Kurihara, Motohashi NAbstract:ESR spectroscopy revealed that 12H-benzo [a]Phenothiazine, 9-methyl-12H-benzo[a]Phenothiazine, 10-methyl- 12H-benzo[a]Phenothiazine, 11-methyl-12H-benzo[a]-Phenothiazine and 5-oxo-5H-benzo[a]Phenothiazine, which induced the differentiation of human myelogenous leukemic cell lines into maturing macrophages, produced radical(s) under an alkaline condition. On the other hand, 6-hydroxy-5-oxo-5H-benzo[a]Phenothiazine, 6-methyl-5-oxo-5H-benzo[a]Phenothiazine and 5H-benzo[a][1,4]benwthiazino-[3,2-c]Phenothiazine, and 13 Phenothiazines, which had little or no differentiation-inducing activity, produced no detectable amounts of radical(s). Using Hiickel molecular orbital (HMO) method, these active benzo[a]Phenothiazines were shown to have the elevated n-spin density at the sulfur atom of their molecules. Seven out of 8 benzo[a]Phenothiazines significantly enhanced the radical intensity of sodium L-ascorbate and sodium 5,6-benzylidene-L-ascorbate (SBA), whereas only 3 out of 13 Phenothiazines showed similar effects. These data suggest that the induction of human leukemic cell differentiation by benzo[a]Phenothiazines might be initiated by radical mediated reactions.
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Antiplasmid activity of Phenothiazines, benzo[a]Phenothiazines and benz[c]acridines.
Anticancer research, 1992Co-Authors: Noboru Motohashi, T Kurihara, Hiroshi Sakagami, K CsuriAbstract:Various synthetic derivatives of Phenothiazines, benzo[a]Phenothiazines and benz[c]acridines were compared for their abilities to induce antiplasmid activity against E. coli F'lac plasmid. Several Phenothiazine derivatives were much more potent in antiplasmid activity than benzo[a]Phenothiazine- or benz[c]acridine derivatives. Their antiplasmid activity seemed to be enhanced by Cl- or CF3- substitution at 2 C atom, and modified by the side chain length and charge at the L-region of the molecules, as well as by hydrophilicity.
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Antimicrobial activity of Phenothiazines, benzo[a]Phenothiazines and benz[c]acridines
Anticancer Research, 1992Co-Authors: Noboru Motohashi, K Csuri, Lajos Ferenczy, T Kurihara, Hiroshi Sakagami, Jozsef MolnarAbstract:The abilities of 14 Phenothiazines, 8 benzo[a]Phenothiazines and 12 benz[c]acridines to induce an antibacterial effect against Escherichia coli K12 were compared. Several Phenothiazines, which showed antiplasmid activity, displayed the most potent antibacterial activity. All benz[c]acridine derivatives were moderately antibacterial, whereas benzo[a]Phenothiazines were inactive. The active Phenothiazine derivatives had more potent inhibitory activity against fungi, including phytopathogen flamentous, human pathogen filamentous fungi and yeasts, than against gram-positive and -negative becteria
Albertina G Moglioni - One of the best experts on this subject based on the ideXlab platform.
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synthesis and antifungal activity of some substituted Phenothiazines and related compounds
European Journal of Medicinal Chemistry, 2011Co-Authors: Gabriela P Sarmiento, Roxana G Vitale, Javier Afeltra, Graciela Y. Moltrasio, Albertina G MoglioniAbstract:Several Phenothiazines and related compounds were synthesized and their antifungal activity was evaluated in vitro. The results observed for α-chloro-N-acetyl Phenothiazine led us to choose this compound as a lead in the search of antifungal agents.
Jozsef Molnar - One of the best experts on this subject based on the ideXlab platform.
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Reversal of ABCB1-related Multidrug Resistance of Colonic Adenocarcinoma Cells by Phenothiazines.
Anticancer Research, 2015Co-Authors: Daniella Takacs, Adam Horvath, Ákos Csonka, Tímea Windt, Leonard Amaral, Gyorgy Hajos, Zsuzsanna Riedl, Jozsef Molnar, Márió Gajdács, Gabriella SpenglerAbstract:BACKGROUND: The most common mechanism that reduces the efficacy of anticancer agents is overexpression of ATP-binding cassette (ABC) drug transporters. Phenothiazines and structurally-related compounds can sensitize multidrug-resistant (MDR) cells to chemotherapeutics. MATERIALS AND METHODS: Phenothiazine derivatives were investigated regarding their anticancer and MDR-reversing effect on colonic adenocarcinoma cells. The anti-proliferative and cytotoxic effects of the derivatives were assessed by the thiazolyl blue tetrazolium bromide (MTT) method, the modulation of the ABCB1 activity was measured by rhodamine 123 accumulation assay using flow cytometry. RESULTS: All Phenothiazines exhibited potent cytotoxic effect on the sensitive and MDR colon adenocarcinoma cell lines. The inhibition of the ABCB1 transporter was greater in the presence of the Phenothiazine derivatives than for the known ABCB1 inhibitor verapamil. CONCLUSION: It can be concluded that these derivatives show synergism in the presence of doxorubicin and could have potential as ABCB1 inhibitors.
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multidrug resistance reversing activity of newly developed Phenothiazines on p glycoprotein abcb1 related resistance of mouse t lymphoma cells
Anticancer Research, 2014Co-Authors: Gabriella Spengler, Daniella Takacs, Adam Horvath, Leonard Amaral, Gyorgy Hajos, Zsuzsanna Riedl, Jozsef MolnarAbstract:Background: Phenothiazines have anticancer properties and are able to reverse the multidrug resistance of neoplastic cells by inhibiting the ATP-binding cassette, sub-family B (MDR/TAP), member 1 protein (ABCB1 or Pglycoprotein) activity. Materials and Methods: A series of new Phenothiazine derivatives was investigated regarding their ABCB1-modulating effect on multidrug resistant mouse T-lymphoma cells by rhodamine 123 accumulation assay and real-time ethidium bromide accumulation assay. Results: The Phenothiazine derivatives exhibited a potent anticancer effect on the parental cell line and on its multidrug-resistant mouse T-lymphoma subline overexpressing the ABCB1 transporter. The inhibition of the ABCB1 transporter in the presence of the newly-developed Phenothiazines was greater than that for the known ABCB1 inhibitors thioridazine and verapamil. Conclusion: Based on the chemical structures and biological activity, compounds with bivalent sulfur atom in the Phenothiazine ring demonstrated marked ABCB1-modulating effect, however, other derivatives with halogen or amide substitutions were ineffective.
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Antitumor activity of Phenothiazine-related compounds
Anticancer Research, 1996Co-Authors: Nagy S, Argyelan G, Masami Kawase, Jozsef Molnar, Motohashi NAbstract:One of the biggest challenges in health care is the fight against tumors. Some Phenothiazines have antitumor activity on HEp-2 tumor cells. In this study, we tested the antitumor effects of three series such as 10-nonsubstituted Phenothiazines, 10-[n-(phthalimido)alkyl]-2-substituted-10H-Phenothiazines and 1-(chloroethyl)-3-(2-substituted-10H-phenothiazin-10-yl)alkyl-1 -- ureas with H, Cl and CF 3 substitution at position C2. The TCID 50 of Phenothiazines was affected by the H, Cl and CF 3 at C2. Trifluoromethyl derivative of Phenothiazine showed potent (R=CF 3 , TCID 50 =4.7 μg) activity, whereas the chlorine derivative of Phenothiazine (R=Cl, TCID 50 =62.5 μg) had a relatively weak effect. In the group of 10-[n-(phthalimido)alkyl]-2-substituted-10H-Phenothiazines, 10-[3-(phthalimidojpropyl]--10H-Phenothiazine (R=H, n=3, TCID 50 =11.5 μg), 10-[4-(phthalimido)butyl]-10H-Phenothiazine (R=H, n=4, TCID 50 =7.8 μg) and 10-[3-(phthalimido)propyl]-2-trifluoromethyl-10H-Phenothiazine (R=CF 3 , n=3, TCID 50 = 11.5 μg) was very effective. On the other hand, TCID 50 of 10-[3-(phthalimido )propyl]-2-chloro-10H-Phenothiazine (R = Cl, n=3, TCID 50 =75.0 μg), 1O-[4-(phthalimido)butyl]-2-chloro-10H-Phenothiazine (R=Cl, n=4, TCID 50 =31.3 μg) and 10-[4-(phthalimido)butyl]-2-trifluoromethyl-10H-Phenothiazine (R=CF 3 , n=4, TCID 50 =50.0 μg) were about 4.8 times less effective than 10-[4-(phthalimido)butyl]-10H-Phenothiazine (R=H, n=4, TCID 50 =7.8 μg). Among six 1-(chloroethyl)-3-(2-substituted-10H-phenothiazin-10-yl)alkyl-1-ureas, two chlorine compounds such as 1-(2-chloroethyl)-3-(2-chloro-10H-phenothiazin-10yl)propyl-1-urea (R=Cl, n=3, TCID 50 =6.3 μg), 1-(2-chloroethyl)-3-(2-chloro-10H-phenothiazin-10-yl) butyl-1-urea (R=Cl, n=4, TCID 50 =78 μg), and 1-(2-chloroethyl)-3-(2-trifluoromethyl-10H-phenothiazin-10-yl)butyl-1-urea (R=CF 3 , n=4, TCID 50 = 78 μg) were significantly active. Tests showed that the substitution at 2C position apparently affected the anti-HEp-2 tumor cell activity ; that the length of the aliphatic side chain at 10N contributes to the anti-tumor activity ; and that the TCID 50 values of the derivatives with butylene group (-C 4 H 8- ) were lower than those with propylene group (-C 3 H 6 -) except 10-[4-(phthalimido) butyl]-2-trifuoromethyl-10H-Phenothiazine and 1-(2-chloroethyl)-3-(2-chloro-10H-pheno-thiazin-10-yl) butyl- 1-urea.
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Antitumor activity of Phenothiazine-related compounds.
Anticancer research, 1996Co-Authors: Nagy S, Argyelan G, Masami Kawase, Jozsef Molnar, Motohashi NAbstract:One of the biggest challenges in health care is the fight against tumors. Some Phenothiazines have antitumor activity on HEp-2 tumor cells. In this study, we tested the antitumor effects of three series such as 10-nonsubstituted Phenothiazines, 10-[n-(phthalimido)alkyl]-2-substituted-10H-Phenothiazines and 1-(chloroethyl)-3-(2-substituted-10H-Phenothiazines-10-yl)alkyl-1-ureas with H, Cl and CF3 substitution at position C2. The TCID50 of Phenothiazines was affected by the H, Cl and CF3 at C2. Trifluoromethyl derivative of Phenothiazine showed potent (R = CF3, TCID50 = 4.7 micrograms) activity, whereas the chlorine derivative of Phenothiazine (R = Cl, TCID50 = 62.5 micrograms) had a relatively weak effect. In the group of 10-[n-(phthalimido)alkyl]-2-substituted-10H-Phenothiazines, 10-[3-(phthalimido)propyl]-10H-Phenothiazine (R = H, n = 3, TCID50 = 11.5 micrograms), 10-[4-(phthalimido)butyl]-10H-Phenothiazine (R = H, n = 4, TCID50 = 7.8 micrograms) and 10-[3-(phthalimido)propyl]-2-trifluoromethyl-10H- Phenothiazine (R = CF3, n = 3, TCID50 = 11.5 micrograms) was very effective. On the other hand, TCID50 of 10-[3-(phthalimido)propyl]-2-chloro-10H-Phenothiazine (R = Cl, n = 3, TCID50 = 75.0 micrograms), 10-[4-(phthalimido)butyl]-2-chloro-10H-Phenothiazine (R = Cl, n = 4, TCID50 = 31.3 micrograms) and 10-[4-(phthalimido)butyl]-2-trifluoromethyl-10H-Phenothiazine (R = CF3, n = 4, TCID50 = 50.0 micrograms) were about 4-8 times less effective than 10-[4-(phthalimido)butyl]-10H-Phenothiazine (R = H, n = 4, TCID50 = 7.8 micrograms). Among six 1-(chloroethyl)-3- (2-substituted-10H-phenothiazin-10-yl)alkyl-1-ureas, two chlorine compounds such as 1-(2-chloroethyl)-3-(2-chloro-10H-phenothiazin-10-yl)propyl-1-urea (R = Cl, n = 3, TCID50 = 6.3 micrograms), 1-(2-chloroethyl)-3-(2-chloro-10H-phenothiazin-10-yl) butyl-1-urea (R = Cl, n = 4, TCID50 = 7.8 micrograms), and 1-(2-chloroethyl)-3-(2-trifluoromethyl-10H-phenothiazin-10-yl)buty l-1-ur ea (R = CF3, n = 4, TCID50 = 7.8 micrograms) were significantly active. Tests showed that the substitution at 2C position apparently affected the anti-HEp-2 tumor cell activity; that the length of the aliphatic side chain at 10N contributes to the anti-tumor activity; and that the TCID50 values of the derivatives with butylene group (-C4H8-) were lower than those with propylene group (-C3H6-) except 10-[4-(phthalimido) butyl]-2-trifuoromethyl-10H-Phenothiazine and 1-(2-chloroethyl)-3-(2-chloro-10H-pheno-thiazin-10-yl) butyl-1-urea.
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Antimicrobial activity of Phenothiazines, benzo[a]Phenothiazines and benz[c]acridines
Anticancer Research, 1992Co-Authors: Noboru Motohashi, K Csuri, Lajos Ferenczy, T Kurihara, Hiroshi Sakagami, Jozsef MolnarAbstract:The abilities of 14 Phenothiazines, 8 benzo[a]Phenothiazines and 12 benz[c]acridines to induce an antibacterial effect against Escherichia coli K12 were compared. Several Phenothiazines, which showed antiplasmid activity, displayed the most potent antibacterial activity. All benz[c]acridine derivatives were moderately antibacterial, whereas benzo[a]Phenothiazines were inactive. The active Phenothiazine derivatives had more potent inhibitory activity against fungi, including phytopathogen flamentous, human pathogen filamentous fungi and yeasts, than against gram-positive and -negative becteria
