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Papers by Marema Makgatho

African health sciences, Apr 1, 2024

Background: The impact of Tuberculosis (TB) places an immense burden on the health care system. I... more Background: The impact of Tuberculosis (TB) places an immense burden on the health care system. Infection with Human Immunodeficiency Virus (HIV) is a significant risk factor in the development and progression of TB disease. Single Nucleotide Polymorphisms (SNPs) in the promoter region of Interleukin-10 (IL-10) and Tumour Necrotic Factor-Alpha (TNF-α) may play a major role in the disease mechanism and understanding these mechanisms might prove to be a useful diagnostic tool in evaluating the immune regulation and progression of the disease. Objective: This study aimed to determine the relationship between cytokine levels and gene variants of Interleukin-10 and Tumour Necrotic Factor Alpha in TB and HIV-infected participants. Methods: Cytokine levels were determined by ELISA, and SNPs were determined by MassArray®. Results: The levels of TNF-α were higher in the TB group than the HIV (p < 0.001) and TB-HIV (p = 0.011) groups, but similar to the TNF-α levels in the control group. In the HIV group, IL-10 levels were higher than those of the TB (p < 0.001) and control groups (p = 0.039), whereas there was no difference between the IL-10 levels in the HIV and the TB-HIV infection groups. The ratio was determined and there were no differences between the four infection groups. In this study, no associations were detected between the circulating plasma levels of TNF-α and IL-10 and their genotypes. Conclusion: Our data showed that the gene variants were not associated with circulating plasma levels of TNF-α and IL-10 in our study population. A pro-inflammatory environment was found in the TB and TB-HIV groups, which is suggesting of bacterial clearance, while an anti-inflammatory environment was found in the HIV group, which suggests the suppression of viral replication.

South African Journal of Science, 1997

African Journal of Traditional, Complementary and Alternative Medicines, 2015

Background: Albizia species including A. gummifera have been used in folk medicine for the treatm... more Background: Albizia species including A. gummifera have been used in folk medicine for the treatment of various conditions by many cultural groups. Apart from its anti-parasitic and antimicrobial activity associated with its use, Albizia gummifera have not been investigated for either its anti-inflammatory properties or anti-proliferative effect in vitro. Materials and Methods: Extracted acetone crude extract of plant material was tested for the presence of various secondary metabolites using chemical tests while the anti-proliferative effect against peripheral blood mononuclear were tested using the WST-1 assay. Nitric oxide production by RAW cell line exposed to extract was also tested using Griess assay as well as the production of interleukin-2 in medium of cultured PMBC using an enzyme-linked-immunosorbent assay (ELISA) kit. Results: Phytochemical testing of acetone leaf extracted was shown to be positive for flavonoids, saponins and tannins. The extract was shown to dose-dependently inhibited proliferation of mononuclear cells while promoting that of RAW cells (p<0.05). The production of IL-2 by mononuclear cells and nitric oxide release by RAW cells were inhibited and stimulated respectively (p<0.05) in both cell types. The extract was also shown to elicit significant anti-and pro-inflammatory potential at concentration above 20 and 40 µg/ml, in both cell types respectively. Conclusion: Further laboratory research is required to elucidate the anti-and pro-inflammatory biochemical pathways as shown by the in vitro immune-modulatory modalities of this plant species. It is also important to further identify bioactive entities of Albizia gummifera responsible for the observed activities.

The in vitro antimalarial activity of clofazimine and seven of its analoques, all TMP(tetramethyl... more The in vitro antimalarial activity of clofazimine and seven of its analoques, all TMP(tetramethyl-piperidyl group)-derivatives except B669, against the RB-1 and pfUP-1 laboratory strains of Plasmodium falciparum was investigated using a flow cytometric procedure. The flow cytometric method was compared with microscopy and radiometry for efficiency in quantitating the level of parasitemia in malaria cultures. The flow cytometric method compared well, as determined by the Bland and Altman measure of agreement, with both microscopy and radiometry (includes a fixing step that allows samples to be evaluated at any one time). The riminophenazine agents were found to exhibit antimalarial action of varying degrees: the B669, B4100, B4103, B4112 and B4158 showed the best activity followed by B4121 and B4169. Clofazimine did not exhibit any activity at concentrations up to 2ug/ml in this system. Their effective concentrations in vitro were comparable to that of standard antimalarial agent chloroquine. The agents B4103 and B4112 exhibited additive antimalarial activities when combined with chloroquine.

Drug Development Research, 2000

ABSTRACT Two novel derivatives of clofazimine [3-(p-chloroanilino)-10-(p-chlorophenyl)-2,10-dihyd... more ABSTRACT Two novel derivatives of clofazimine [3-(p-chloroanilino)-10-(p-chlorophenyl)-2,10-dihydro-2-isopropylimino)phenazine] and the tetramethylpiperidine (TMP)-substituted phenazines, B4119 [3-(3-chloro-4-fluoroanilino)-10-(3-chloro-4-fluorophenyl)-2,10-dihydro-2(2,2,6,6-tetramethylpiper-4-ylimino)phenazine] and B4158 [3-(4-isopropylanilino)-10-(4-isopropylphenyl)-2,10-dihydro-2-(2,2,6,6-tetramethylpiper-4-ylimino)phenazine] (1–8 μM), were evaluated for activity against chloroquin-, quinine-, and sulfadoxine/pyrimethamine-sensitive and -resistant strains of Plasmodium falciparum in vitro, as well as for their effects on polymerisation of haeme to β-hematin. By using microscopic and flow cytometric methods, it was found that B4119 and B4158, but not clofazimine, inhibited the growth of sensitive, as well as resistant strains of P. falciparum with IC50 values between 0.22 and 0.7 μM, indicating lack of cross-resistance. Augmentation of anti-plasmodial activity was observed when B4119 and B4158 were used in combination with chloroquin or mefloquine. Inhibition of the growth of P. falciparum was associated with interference with haeme polymerisation to β-hematin in vitro, while administration of B4119 to P. berghei-infected mice was accompanied by a significant reduction in parasitemia and improved therapeutic activity was observed when this agent was combined with chloroquin. The data presented in this study demonstrate that the TMP-substitution at position 2 on the phenazine nucleus of riminophenazines confers anti-plasmodial activity on these compounds. These may prove to be useful forerunners in the design of novel anti-plasmodial pharmacologic agents. Drug Dev. Res. 50:195–202, 2000. © 2000 Wiley-Liss, Inc.

African Health Sciences

Background: Tetramethyl-piperidine-substituted, B4119 and B4158 have been shown to exhibit antipl... more Background: Tetramethyl-piperidine-substituted, B4119 and B4158 have been shown to exhibit antiplasmodial activity. Objectives: The in vitro antiplasmodial, cytotoxic and oxidative activities of clofazimine and its analogues, all TMP (tetramethylpiperidyl)-substituted phenazines except B669, were evaluated in this study. Methods: The antiplasmodial activity of the compounds against RB-1 and pfUP10 laboratory strains of Plasmodium falciparum was investigated by flow cytometry. The cytotoxic activity against HeLa cells and oxidative activity were studied employing colorimetric and cytochrome C reduction assays respectively. Results: The riminophenazine agents exhibited antiplasmodial action of varying degrees: B669, B4100 and B4103 showed the best activity while B4121 and B4169 exhibited significant activity at 2µg/ml. Clofazimine had no antiplasmodial activity. The compounds B4100, B4103, B4121 and B4169 exhibited significant cytotoxic activity against HeLa cells at concentrations of 0.5µg/ml and above while B669 was active at 2µg/ml. Clofazimine and B669 tested at a concentration of 0.5µg/ml caused enhancement (p ≤ 0.05) of neutrophil superoxide production when compared to the FMLP control while all the other TMP-derivatives had no effect (p ≥ 0.05). Conclusion: Tetramethylpiperidyl-subsituted phenazines may potentially be useful antimalarial/antitumor agents with no pro-oxidative properties. In vivo studies on the agents relative to these properties are recommended.

African Health Sciences

Background: Cervical cancer is common in women in less developed regions of the world. The plant ... more Background: Cervical cancer is common in women in less developed regions of the world. The plant biomolecules can be employed for synergistic activity with chemo- and radiotherapy. This combinations might result in reduced toxicity and increased efficacy of the treatment regimen. Objectives: The anti-HeLa cells activity of the acetone extracts of S. plumosum, T. cilliata and S. pinnata was assessed using different parameters. Methods: Secondary metabolite detection and antioxidant activity quantification were determined using the DPPH and ferric iron reducing assays. HeLa cell growth inhibition and mechanistics were assessed by employing MTT and Annexin-V flous assays. Results: Observations revealed the presence of phenolic, flavonoids, tannins steroids and coumarins in all the plants ex- tracts. High amount of total phenolic and flavonoid content were detected in S. plumosum and T. cilliata. S. plumosum extract had the best DPPH scavenging activity and ferric reducing powers. Concl...

African Health Sciences, 2016

Background: Malaria is on the increase due to emergence of parasite drug resistance and there is ... more Background: Malaria is on the increase due to emergence of parasite drug resistance and there is thus an urgent need for the development of new antiparasitic drugs effective at low concentrations. Ketolides antibiotics are used for treatment of various ailments and are relevant candidates to establish antiparasitic activity. Objectives: The present study investigates the activity of ketolide compounds HMR 3004 and HMR 3647 (telithromycin) (0.025-12.5 µM) for activity against chloroquine-sensitive and resistant strains of Plasmodium falciparum in vitro. Methods: The antiplasmodial activity of the two ketolide agents were determined using microscopic and colorimetric [lactate dehydrogenase assay] procedures. Results: Both HMR 3004 and HMR 3647 caused a dose-dependent inhibition of growth of both parasite strains with IC50 values 3 and 15 nM, respectively. Suppression of parasite growth was evident after 8 hours of exposure to both agents at 12.5 µM with total parasite clearance achieved at 40 hours.

African Health Sciences, 2016

Background: Malaria is on the increase due to emergence of parasite drug resistance and there is ... more Background: Malaria is on the increase due to emergence of parasite drug resistance and there is thus an urgent need for the development of new antiparasitic drugs effective at low concentrations. Ketolides antibiotics are used for treatment of various ailments and are relevant candidates to establish antiparasitic activity. Objectives: The present study investigates the activity of ketolide compounds HMR 3004 and HMR 3647 (telithromycin) (0.025-12.5 µM) for activity against chloroquine-sensitive and resistant strains of Plasmodium falciparum in vitro. Methods: The antiplasmodial activity of the two ketolide agents were determined using microscopic and colorimetric [lactate dehydrogenase assay] procedures. Results: Both HMR 3004 and HMR 3647 caused a dose-dependent inhibition of growth of both parasite strains with IC50 values 3 and 15 nM, respectively. Suppression of parasite growth was evident after 8 hours of exposure to both agents at 12.5 µM with total parasite clearance achieved at 40 hours.

Drug Development Research, 2000

ABSTRACT Two novel derivatives of clofazimine [3-(p-chloroanilino)-10-(p-chlorophenyl)-2,10-dihyd... more ABSTRACT Two novel derivatives of clofazimine [3-(p-chloroanilino)-10-(p-chlorophenyl)-2,10-dihydro-2-isopropylimino)phenazine] and the tetramethylpiperidine (TMP)-substituted phenazines, B4119 [3-(3-chloro-4-fluoroanilino)-10-(3-chloro-4-fluorophenyl)-2,10-dihydro-2(2,2,6,6-tetramethylpiper-4-ylimino)phenazine] and B4158 [3-(4-isopropylanilino)-10-(4-isopropylphenyl)-2,10-dihydro-2-(2,2,6,6-tetramethylpiper-4-ylimino)phenazine] (1–8 μM), were evaluated for activity against chloroquin-, quinine-, and sulfadoxine/pyrimethamine-sensitive and -resistant strains of Plasmodium falciparum in vitro, as well as for their effects on polymerisation of haeme to β-hematin. By using microscopic and flow cytometric methods, it was found that B4119 and B4158, but not clofazimine, inhibited the growth of sensitive, as well as resistant strains of P. falciparum with IC50 values between 0.22 and 0.7 μM, indicating lack of cross-resistance. Augmentation of anti-plasmodial activity was observed when B4119 and B4158 were used in combination with chloroquin or mefloquine. Inhibition of the growth of P. falciparum was associated with interference with haeme polymerisation to β-hematin in vitro, while administration of B4119 to P. berghei-infected mice was accompanied by a significant reduction in parasitemia and improved therapeutic activity was observed when this agent was combined with chloroquin. The data presented in this study demonstrate that the TMP-substitution at position 2 on the phenazine nucleus of riminophenazines confers anti-plasmodial activity on these compounds. These may prove to be useful forerunners in the design of novel anti-plasmodial pharmacologic agents. Drug Dev. Res. 50:195–202, 2000. © 2000 Wiley-Liss, Inc.

African health sciences, Apr 1, 2024

Background: The impact of Tuberculosis (TB) places an immense burden on the health care system. I... more Background: The impact of Tuberculosis (TB) places an immense burden on the health care system. Infection with Human Immunodeficiency Virus (HIV) is a significant risk factor in the development and progression of TB disease. Single Nucleotide Polymorphisms (SNPs) in the promoter region of Interleukin-10 (IL-10) and Tumour Necrotic Factor-Alpha (TNF-α) may play a major role in the disease mechanism and understanding these mechanisms might prove to be a useful diagnostic tool in evaluating the immune regulation and progression of the disease. Objective: This study aimed to determine the relationship between cytokine levels and gene variants of Interleukin-10 and Tumour Necrotic Factor Alpha in TB and HIV-infected participants. Methods: Cytokine levels were determined by ELISA, and SNPs were determined by MassArray®. Results: The levels of TNF-α were higher in the TB group than the HIV (p < 0.001) and TB-HIV (p = 0.011) groups, but similar to the TNF-α levels in the control group. In the HIV group, IL-10 levels were higher than those of the TB (p < 0.001) and control groups (p = 0.039), whereas there was no difference between the IL-10 levels in the HIV and the TB-HIV infection groups. The ratio was determined and there were no differences between the four infection groups. In this study, no associations were detected between the circulating plasma levels of TNF-α and IL-10 and their genotypes. Conclusion: Our data showed that the gene variants were not associated with circulating plasma levels of TNF-α and IL-10 in our study population. A pro-inflammatory environment was found in the TB and TB-HIV groups, which is suggesting of bacterial clearance, while an anti-inflammatory environment was found in the HIV group, which suggests the suppression of viral replication.

South African Journal of Science, 1997

African Journal of Traditional, Complementary and Alternative Medicines, 2015

Background: Albizia species including A. gummifera have been used in folk medicine for the treatm... more Background: Albizia species including A. gummifera have been used in folk medicine for the treatment of various conditions by many cultural groups. Apart from its anti-parasitic and antimicrobial activity associated with its use, Albizia gummifera have not been investigated for either its anti-inflammatory properties or anti-proliferative effect in vitro. Materials and Methods: Extracted acetone crude extract of plant material was tested for the presence of various secondary metabolites using chemical tests while the anti-proliferative effect against peripheral blood mononuclear were tested using the WST-1 assay. Nitric oxide production by RAW cell line exposed to extract was also tested using Griess assay as well as the production of interleukin-2 in medium of cultured PMBC using an enzyme-linked-immunosorbent assay (ELISA) kit. Results: Phytochemical testing of acetone leaf extracted was shown to be positive for flavonoids, saponins and tannins. The extract was shown to dose-dependently inhibited proliferation of mononuclear cells while promoting that of RAW cells (p<0.05). The production of IL-2 by mononuclear cells and nitric oxide release by RAW cells were inhibited and stimulated respectively (p<0.05) in both cell types. The extract was also shown to elicit significant anti-and pro-inflammatory potential at concentration above 20 and 40 µg/ml, in both cell types respectively. Conclusion: Further laboratory research is required to elucidate the anti-and pro-inflammatory biochemical pathways as shown by the in vitro immune-modulatory modalities of this plant species. It is also important to further identify bioactive entities of Albizia gummifera responsible for the observed activities.

The in vitro antimalarial activity of clofazimine and seven of its analoques, all TMP(tetramethyl... more The in vitro antimalarial activity of clofazimine and seven of its analoques, all TMP(tetramethyl-piperidyl group)-derivatives except B669, against the RB-1 and pfUP-1 laboratory strains of Plasmodium falciparum was investigated using a flow cytometric procedure. The flow cytometric method was compared with microscopy and radiometry for efficiency in quantitating the level of parasitemia in malaria cultures. The flow cytometric method compared well, as determined by the Bland and Altman measure of agreement, with both microscopy and radiometry (includes a fixing step that allows samples to be evaluated at any one time). The riminophenazine agents were found to exhibit antimalarial action of varying degrees: the B669, B4100, B4103, B4112 and B4158 showed the best activity followed by B4121 and B4169. Clofazimine did not exhibit any activity at concentrations up to 2ug/ml in this system. Their effective concentrations in vitro were comparable to that of standard antimalarial agent chloroquine. The agents B4103 and B4112 exhibited additive antimalarial activities when combined with chloroquine.

Drug Development Research, 2000

ABSTRACT Two novel derivatives of clofazimine [3-(p-chloroanilino)-10-(p-chlorophenyl)-2,10-dihyd... more ABSTRACT Two novel derivatives of clofazimine [3-(p-chloroanilino)-10-(p-chlorophenyl)-2,10-dihydro-2-isopropylimino)phenazine] and the tetramethylpiperidine (TMP)-substituted phenazines, B4119 [3-(3-chloro-4-fluoroanilino)-10-(3-chloro-4-fluorophenyl)-2,10-dihydro-2(2,2,6,6-tetramethylpiper-4-ylimino)phenazine] and B4158 [3-(4-isopropylanilino)-10-(4-isopropylphenyl)-2,10-dihydro-2-(2,2,6,6-tetramethylpiper-4-ylimino)phenazine] (1–8 μM), were evaluated for activity against chloroquin-, quinine-, and sulfadoxine/pyrimethamine-sensitive and -resistant strains of Plasmodium falciparum in vitro, as well as for their effects on polymerisation of haeme to β-hematin. By using microscopic and flow cytometric methods, it was found that B4119 and B4158, but not clofazimine, inhibited the growth of sensitive, as well as resistant strains of P. falciparum with IC50 values between 0.22 and 0.7 μM, indicating lack of cross-resistance. Augmentation of anti-plasmodial activity was observed when B4119 and B4158 were used in combination with chloroquin or mefloquine. Inhibition of the growth of P. falciparum was associated with interference with haeme polymerisation to β-hematin in vitro, while administration of B4119 to P. berghei-infected mice was accompanied by a significant reduction in parasitemia and improved therapeutic activity was observed when this agent was combined with chloroquin. The data presented in this study demonstrate that the TMP-substitution at position 2 on the phenazine nucleus of riminophenazines confers anti-plasmodial activity on these compounds. These may prove to be useful forerunners in the design of novel anti-plasmodial pharmacologic agents. Drug Dev. Res. 50:195–202, 2000. © 2000 Wiley-Liss, Inc.

African Health Sciences

Background: Tetramethyl-piperidine-substituted, B4119 and B4158 have been shown to exhibit antipl... more Background: Tetramethyl-piperidine-substituted, B4119 and B4158 have been shown to exhibit antiplasmodial activity. Objectives: The in vitro antiplasmodial, cytotoxic and oxidative activities of clofazimine and its analogues, all TMP (tetramethylpiperidyl)-substituted phenazines except B669, were evaluated in this study. Methods: The antiplasmodial activity of the compounds against RB-1 and pfUP10 laboratory strains of Plasmodium falciparum was investigated by flow cytometry. The cytotoxic activity against HeLa cells and oxidative activity were studied employing colorimetric and cytochrome C reduction assays respectively. Results: The riminophenazine agents exhibited antiplasmodial action of varying degrees: B669, B4100 and B4103 showed the best activity while B4121 and B4169 exhibited significant activity at 2µg/ml. Clofazimine had no antiplasmodial activity. The compounds B4100, B4103, B4121 and B4169 exhibited significant cytotoxic activity against HeLa cells at concentrations of 0.5µg/ml and above while B669 was active at 2µg/ml. Clofazimine and B669 tested at a concentration of 0.5µg/ml caused enhancement (p ≤ 0.05) of neutrophil superoxide production when compared to the FMLP control while all the other TMP-derivatives had no effect (p ≥ 0.05). Conclusion: Tetramethylpiperidyl-subsituted phenazines may potentially be useful antimalarial/antitumor agents with no pro-oxidative properties. In vivo studies on the agents relative to these properties are recommended.

African Health Sciences

Background: Cervical cancer is common in women in less developed regions of the world. The plant ... more Background: Cervical cancer is common in women in less developed regions of the world. The plant biomolecules can be employed for synergistic activity with chemo- and radiotherapy. This combinations might result in reduced toxicity and increased efficacy of the treatment regimen. Objectives: The anti-HeLa cells activity of the acetone extracts of S. plumosum, T. cilliata and S. pinnata was assessed using different parameters. Methods: Secondary metabolite detection and antioxidant activity quantification were determined using the DPPH and ferric iron reducing assays. HeLa cell growth inhibition and mechanistics were assessed by employing MTT and Annexin-V flous assays. Results: Observations revealed the presence of phenolic, flavonoids, tannins steroids and coumarins in all the plants ex- tracts. High amount of total phenolic and flavonoid content were detected in S. plumosum and T. cilliata. S. plumosum extract had the best DPPH scavenging activity and ferric reducing powers. Concl...

African Health Sciences, 2016

Background: Malaria is on the increase due to emergence of parasite drug resistance and there is ... more Background: Malaria is on the increase due to emergence of parasite drug resistance and there is thus an urgent need for the development of new antiparasitic drugs effective at low concentrations. Ketolides antibiotics are used for treatment of various ailments and are relevant candidates to establish antiparasitic activity. Objectives: The present study investigates the activity of ketolide compounds HMR 3004 and HMR 3647 (telithromycin) (0.025-12.5 µM) for activity against chloroquine-sensitive and resistant strains of Plasmodium falciparum in vitro. Methods: The antiplasmodial activity of the two ketolide agents were determined using microscopic and colorimetric [lactate dehydrogenase assay] procedures. Results: Both HMR 3004 and HMR 3647 caused a dose-dependent inhibition of growth of both parasite strains with IC50 values 3 and 15 nM, respectively. Suppression of parasite growth was evident after 8 hours of exposure to both agents at 12.5 µM with total parasite clearance achieved at 40 hours.

African Health Sciences, 2016

Background: Malaria is on the increase due to emergence of parasite drug resistance and there is ... more Background: Malaria is on the increase due to emergence of parasite drug resistance and there is thus an urgent need for the development of new antiparasitic drugs effective at low concentrations. Ketolides antibiotics are used for treatment of various ailments and are relevant candidates to establish antiparasitic activity. Objectives: The present study investigates the activity of ketolide compounds HMR 3004 and HMR 3647 (telithromycin) (0.025-12.5 µM) for activity against chloroquine-sensitive and resistant strains of Plasmodium falciparum in vitro. Methods: The antiplasmodial activity of the two ketolide agents were determined using microscopic and colorimetric [lactate dehydrogenase assay] procedures. Results: Both HMR 3004 and HMR 3647 caused a dose-dependent inhibition of growth of both parasite strains with IC50 values 3 and 15 nM, respectively. Suppression of parasite growth was evident after 8 hours of exposure to both agents at 12.5 µM with total parasite clearance achieved at 40 hours.

Drug Development Research, 2000

ABSTRACT Two novel derivatives of clofazimine [3-(p-chloroanilino)-10-(p-chlorophenyl)-2,10-dihyd... more ABSTRACT Two novel derivatives of clofazimine [3-(p-chloroanilino)-10-(p-chlorophenyl)-2,10-dihydro-2-isopropylimino)phenazine] and the tetramethylpiperidine (TMP)-substituted phenazines, B4119 [3-(3-chloro-4-fluoroanilino)-10-(3-chloro-4-fluorophenyl)-2,10-dihydro-2(2,2,6,6-tetramethylpiper-4-ylimino)phenazine] and B4158 [3-(4-isopropylanilino)-10-(4-isopropylphenyl)-2,10-dihydro-2-(2,2,6,6-tetramethylpiper-4-ylimino)phenazine] (1–8 μM), were evaluated for activity against chloroquin-, quinine-, and sulfadoxine/pyrimethamine-sensitive and -resistant strains of Plasmodium falciparum in vitro, as well as for their effects on polymerisation of haeme to β-hematin. By using microscopic and flow cytometric methods, it was found that B4119 and B4158, but not clofazimine, inhibited the growth of sensitive, as well as resistant strains of P. falciparum with IC50 values between 0.22 and 0.7 μM, indicating lack of cross-resistance. Augmentation of anti-plasmodial activity was observed when B4119 and B4158 were used in combination with chloroquin or mefloquine. Inhibition of the growth of P. falciparum was associated with interference with haeme polymerisation to β-hematin in vitro, while administration of B4119 to P. berghei-infected mice was accompanied by a significant reduction in parasitemia and improved therapeutic activity was observed when this agent was combined with chloroquin. The data presented in this study demonstrate that the TMP-substitution at position 2 on the phenazine nucleus of riminophenazines confers anti-plasmodial activity on these compounds. These may prove to be useful forerunners in the design of novel anti-plasmodial pharmacologic agents. Drug Dev. Res. 50:195–202, 2000. © 2000 Wiley-Liss, Inc.