Carbonic anhydrase inhibitors: Inhibition of Plasmodium falciparum carbonic anhydrase with aromatic/heterocyclic sulfonamides—in vitro and in vivo studies

The pathogenicity of Plasmodium falciparum (Pf) malaria results from the stiffening of red blood cells (RBCs) and its ability to adhere to endothelial cells (cytoadherence). The dynamics of Pf-parasitized RBCs is studied by three-dimensional mesoscopic simulations of flow in cylindrical capillaries in order to predict the flow resistance enhancement at different parasitemia levels. In addition, the adhesive dynamics of Pf-RBCs is explored for various parameters revealing several types of cell dynamics such as firm adhesion, very slow slipping along the wall, and intermittent flipping. The parasite inside the RBC is modeled explicitly in order to capture phenomena such as “hindered tumbling” motion of the RBC and the sudden transition from firm RBC cytoadherence to flipping on the endothelial surface. These predictions are in quantitative agreement with recent experimental observations, and thus the three-dimensional modeling method presented here provides new capabilities for guiding and interpreting future in vitro and in vivo studies of malaria.

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Sulphonamide Carbonic Anhydrase Inhibitors and Intra-Ocular Pressure in Rabbits. A comparison between in vitro and in vivo activities based on tissue distributions and physical and chemical properties of nine compounds.

Acta Pharmacologica et Toxicologica ◽

10.1111/j.1600-0773.1961.tb01653.x ◽

2009 ◽

Vol 17 (4) ◽

pp. 337-355 ◽

Cited By ~ 32

Author(s):

Per J. Wistrand ◽

James A. Rawls ◽

Thomas H. Maren

Keyword(s):

Carbonic Anhydrase ◽

Chemical Properties ◽

Physical And Chemical Properties ◽

Carbonic Anhydrase Inhibitors ◽

Intra Ocular Pressure ◽

Ocular Pressure ◽

Physical And Chemical ◽

And Chemical Properties

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Upregulation of ICAM-I by Plasmodium falciparum: in vitro and in vivo studies.

Journal of Clinical Pathology ◽

10.1136/jcp.47.7.653 ◽

1994 ◽

Vol 47 (7) ◽

pp. 653-656 ◽

Cited By ~ 11

Author(s):

W Graninger ◽

J Prada ◽

S Neifer ◽

G Zotter ◽

F Thalhammer ◽

...

Keyword(s):

Plasmodium Falciparum ◽

In Vivo Studies

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Effect of Solanun nudum Extracts on the Liver of Mice Infected with Plasmodium berghei

The American Journal of Chinese Medicine ◽

10.1142/s0192415x01000496 ◽

2001 ◽

Vol 29 (03n04) ◽

pp. 477-484 ◽

Cited By ~ 9

Author(s):

Echeverri Marcela ◽

Blair Silvia ◽

Carmona Jaime ◽

Pérez Pilar

Keyword(s):

Plasmodium Falciparum ◽

Therapeutic Effect ◽

Aqueous Extract ◽

Plasmodium Berghei ◽

Antimalarial Activity ◽

In Vivo Studies ◽

Hexane Extracts ◽

Liver Changes

The plant Solanum nudum has been used by the community of Tumaco (Nariño, Colombia) as a cure for malaria. Our group has confirmed the in vitro antimalarial activity against the strain of Plasmodium falciparum FCB-2. During our in vivo studies on the therapeutic effect of Solanum nudum extracts on mice infected with Plasmodium berghei, we observed yellowish tint in the palms of mice treated with the aqueous extract via ip at a concentration of 2.4% w/vol. This findings suggested the need to carry out a histology study of the liver. Plasmodium berghei infection produces liver changes such as the deposit of pigment inn sinusoids, leucocytes infiltration, esteatosis and necrosis of hepatocytes. These changes were also observed when the mice were treated with methane and hexane extracts from Solanum nudum; however necrosis of hepatocytes in mice infected with malaria decreased 47–65% when they were administered wither with queous extract, or tumacoside A and degraded diosgenone, compounds from methane and hexane extracts of Solanum nudum respectively.

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Discovery of Potent Carbonic Anhydrase Inhibitors as Effective Anticonvulsant Agents: Drug Design, Synthesis, and In Vitro and In Vivo Investigations

Journal of Medicinal Chemistry ◽

10.1021/acs.jmedchem.0c01889 ◽

2021 ◽

Author(s):

Chandra Bhushan Mishra ◽

Shikha Kumari ◽

Andrea Angeli ◽

Silvia Bua ◽

Raj Kumar Mongre ◽

...

Keyword(s):

Drug Design ◽

Carbonic Anhydrase ◽

Carbonic Anhydrase Inhibitors ◽

Design Synthesis ◽

Anticonvulsant Agents

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Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100162132 ◽

1990 ◽

Vol 48 (3) ◽

pp. 914-915

Author(s):

D.J.P. Ferguson ◽

A.R. Berendt ◽

J. Tansey ◽

K. Marsh ◽

C.I. Newbold

Keyword(s):

Plasmodium Falciparum ◽

Red Blood Cells ◽

Blood Cells ◽

Umbilical Vein ◽

Cell Types ◽

Amelanotic Melanoma ◽

Cytoplasmic Process ◽

Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

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