In silico analysis for factors affecting anti-malarial penetration into red blood cells

Abstract

Background: Malaria is a parasitic disease that produces significant infection in red blood cells. The objective of this study is to investigate the relationships between factors affecting the penetration of currently available anti-malarials into red blood cells. Methods: Fifteen anti-malarial drugs listed in the third edition of the World Health Organization malaria treatment guidelines were enrolled in the study. Relationship analysis began with the prioritization of the physicochemical properties of the anti-malarials to create a multivariate linear regression model that correlates the red blood cell penetration. Results: It was found that protein binding was significantly correlated with red blood cell penetration, with a negative coefficient. The next step was repeated analysis to find molecular descriptors that influence protein binding. The coefficients of the number of rotating bonds and the number of aliphatic hydrocarbons are negative, as opposed to the positive coefficients of the number of hydrogen bonds and the number of aromatic hydrocarbons. The p-value was less than 0.05. Conclusions: Anti-malarials with a small number of hydrogen bonds and aromatic hydrocarbons, together with a high number of rotatable bonds and aliphatic hydrocarbons, may have a higher tendency to penetrate the red blood cells.

Effects of low temperature on blood‐to‐plasma ratio measurement

“…R b spans a wide range of values from 0.7 to 76 (100‐fold). The R b data obtained at 37°C within this study are largely consistent with those reported in the literature (Berry et al., 2011; Hinderling, 1997; “https://didb.druginteractionsolutions.org/,”; Pornputtapong et al, 2020; Yu et al., 2005). The comparison plot of R b between 37°C and 4°C is shown in Figure 1.…”

In Silico Study Chitosan Snail Shell as Antioxidant Through Interesting NRF2-KEAP1 in Hypercholesterolemia

“…Hydrophobic interactions avoid a liquid environment and tend to cluster within the globular structure of proteins. The results of this study are by several previous studies which stated that drug candidates generally have the number of hydrogen bonding bonds [14][15][16] , because the average number of hydrophobic atoms in drugs is generally 16 , with one to two donors and three to four acceptors 17 , so that hydrophobic interactions play an important role in drug candidates because they can increase the binding affinity between target interfaces. The in silico test proved that the binding affinity and drug efficacy associated with hydrophobic bonds could be optimized by combining them at the hydrogen bond site 18,19 .…”

Histidinal‐Based Potent Antimalarial Agents

“…For a majority of the compounds, including the most potent ones, the ClogP value was <5, suggesting that they are hydrophilic and readily bioavailable. Further, the lower ClogP values also suggest better membrane permeability and entry into red blood cells [25b–c] . The calculated ClogP values for the most potent compounds in the series‐2: 8 e , 8 g , and 8 h (EC 50 values: 0.43, 0.018, and 0.069 μM) are 2.54, 2.39, and 4.30, respectively.…”