β-Carboline Derivatives Tackling Malaria: Biological Evaluation and Docking Analysis

Gorki, Varun; Walter, Neha Sylvia; Singh, R. D.; Chauhan, Monika; Dhingra, Neelima; Salunke, Deepak B.; Kaur, Sukhbir

doi:10.1021/acsomega.0c01256

Cited by 32 publications

(16 citation statements)

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“…To study various aspects of mammalian malaria, such as developmental biology, interactions between the parasite and its host, development of vaccines, and testing of novel drug candidates, rodent-infecting Plasmodium species are recognized as valuable experimental models as they have a conserved genome organization, basic biology, housekeeping genes and biochemical processes, as well as characteristic patterns of drug sensitivity and resistance that are similar to human-infecting species of Plasmodium . 22 23 Hence, P. berghei (NK-65) is the experimental model used for carrying out drug screening assays because P. falciparum cannot be maintained in rodents.…”

Section: Discussionmentioning

confidence: 99%

Preparation, Standardization and Anti-plasmodial Efficacy of Novel Malaria Nosodes

et al. 2021

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Background Resistance to artemisinin and its partner drugs has threatened the sustainability of continuing the global efforts to curb malaria, which urges the need to look for newer therapies to control the disease without any adverse side effects. In the present study, novel homeopathic nosodes were prepared from Plasmodium falciparum and also assessed for their in vitro and in vivo anti-plasmodial activity. Methods Three nosodes were prepared from P. falciparum (chloroquine [CQ]-sensitive [3D7] and CQ-resistant [RKL-9] strains) as per the Homeopathic Pharmacopoeia of India, viz. cell-free parasite nosode, infected RBCs nosode, mixture nosode. In vitro anti-malarial activity was assessed by schizont maturation inhibition assay. The in vitro cytotoxicity was evaluated by MTT assay. Knight and Peter's method was used to determine in vivo suppressive activity. Mice were inoculated with P. berghei-infected erythrocytes on day 1 and treatment was initiated on the same day. Biochemical, cytokine and histopathological analyses were carried out using standard methods. Results In vitro: the nosodes exhibited considerable activity against P. falciparum with maximum 71.42% (3D7) and 68.57% (RKL-9) inhibition by mixture nosode followed by cell-free parasite nosode (62.85% 3D7 and 60% RKL-9) and infected RBCs nosode (60.61% 3D7 and 57.14% RKL-9). The nosodes were non-toxic to RAW macrophage cell line with >70% cell viability. In vivo: Considerable suppressive efficacy was observed in mixture nosode-treated mice, with 0.005 ± 0.001% parasitemia on day 35. Levels of liver and kidney function biomarkers were within the normal range in the mixture nosode-treated groups. Cytokine analysis revealed increased levels of IL-4 and IL-10, whilst a decline in IL-17 and IFN-γ was evident in the mixture nosode-treated mice. Conclusion The mixture nosode exhibited promising anti-malarial activity against P. falciparum and P. berghei. Biochemical and histopathological studies also highlighted the safety of the nosode for the rodent host. The study provides valuable insight into a novel medicament that has potential for use in the treatment of malaria.

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Section: Discussionmentioning

confidence: 99%

Preparation, Standardization and Anti-plasmodial Efficacy of Novel Malaria Nosodes

et al. 2021

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“…Increase in ALP , bilirubin, SGOT and SGPT in malaria-infected individuals is an indication of liver dysfunction. Gorki et al [27, 28] reported elevated ALP, SGOT, SGPT and bilirubin levels in the infected control as compared to normal mice. The results of the present study are in agreement with these reports as significantly elevated ALP, SGOT, SGPT and bilirubin levels were observed in the infected control as compared to normal mice.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Chininum Sulphuricum 30C against Malaria: An in vitro and in vivo Study

et al. 2021

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Background: New effective, economical and safe antimalarial drugs are urgently needed due to the development of multi-drug-resistant strains of the parasite. Homeopathy uses ultra-diluted doses of various substances to stimulate autoregulatory and self-healing processes to cure various ailments. The aim of the study was to evaluate the in vitro and in vivo antimalarial efficacy of a homeopathic drug, Chininum sulphuricum 30C. Methods: In vitro antiplasmodial activity was screened against the P. falciparum chloroquine-sensitive (3D7) strain, and cell viability was assessed against normal human dermal fibroblasts and HepG2 cells. Suppressive, preventive and curative studies were carried out against P. berghei-infected mice in vivo. Results: Chininum sulphuricum (30C) revealed good antiplasmodial activity in vitro, with 92.79 ± 6.93% inhibition against the 3D7 strain. The cell viability was 83.6 ± 0.6% against normal human dermal fibroblasts and 95.22 ± 5.1% against HepG2 cells. It also exhibited suppressive efficacy with 95.56% chemosuppression on day 7 with no mortality throughout the follow-up period of 28 days. It also showed preventive activity against the disease. Drug treatment was also safe to the liver and kidney function of the host as evidenced by biochemical studies. Conclusion: Chininum sulphuricum 30C exhibited considerable antimalarial activity along with safety to the liver and kidney function of the host.

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“…Several reviews addressed the anticancer activity of β-carboline derivatives and proposed different modes of action [ 9 , 15 , 17 ]. Similarly, the antimalarial activity of harmine and other β-carboline derivatives is also well-documented [ 18 , 19 , 20 ]. On the other hand, ferrocene is an important compound in bioinorganometallic chemistry due to its high stability, favorable redox properties, and low toxicity [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Harmicens, Novel Harmine and Ferrocene Hybrids: Design, Synthesis and Biological Activity

Poje

Marinović

Pavić

et al. 2022

IJMS

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Cancer and malaria are both global health threats. Due to the increase in the resistance to the known drugs, research on new active substances is a priority. Here, we present the design, synthesis, and evaluation of the biological activity of harmicens, hybrids composed of covalently bound harmine/β-carboline and ferrocene scaffolds. Structural diversity was achieved by varying the type and length of the linker between the β-carboline ring and ferrocene, as well as its position on the β-carboline ring. Triazole-type harmicens were prepared using Cu(I)-catalyzed azide-alkyne cycloaddition, while the synthesis of amide-type harmicens was carried out by applying a standard coupling reaction. The results of in vitro biological assays showed that the harmicens exerted moderate antiplasmodial activity against the erythrocytic stage of P. falciparum (IC50 in submicromolar and low micromolar range) and significant and selective antiproliferative activity against the MCF-7 and HCT116 cell lines (IC50 in the single-digit micromolar range, SI > 5.9). Cell localization experiments showed different localizations of nonselective harmicene 36 and HCT116-selective compound 28, which clearly entered the nucleus. A cell cycle analysis revealed that selective harmicene 28 had already induced G1 cell cycle arrest after 24 h, followed by G2/M arrest with a concomitant drastic reduction in the percentage of cells in the S phase, whereas the effect of nonselective compound 36 on the cell cycle was much less pronounced, which agreed with their different localizations within the cell.

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β-Carboline Derivatives Tackling Malaria: Biological Evaluation and Docking Analysis

Cited by 32 publications

References 55 publications

Preparation, Standardization and Anti-plasmodial Efficacy of Novel Malaria Nosodes

Preparation, Standardization and Anti-plasmodial Efficacy of Novel Malaria Nosodes

Efficacy of Chininum Sulphuricum 30C against Malaria: An in vitro and in vivo Study

Harmicens, Novel Harmine and Ferrocene Hybrids: Design, Synthesis and Biological Activity

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