Assessment of Lipophilicity Parameters of Antimicrobial and Immunosuppressive Compounds

Wardecki, Dawid; Dołowy, Małgorzata; Bober-Majnusz, Katarzyna

doi:10.3390/molecules28062820

Cited by 7 publications

(2 citation statements)

References 39 publications

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“…It is worth noting that the experimental lipophilicity values (RmoExper) better explain the antibacterial activity than the calculated lipophilicity (miLOGP) values (only two selections in Table S26). This agrees with the suggestions of authors investigating this lipophilicity phenomenon using computational and chromatography methods [32,42].…”

supporting

confidence: 93%

Modeling of Effectiveness of N3-Substituted Amidrazone Derivatives as Potential Agents against Gram-Positive Bacteria

Ćwiklińska-Jurkowska,

Paprocka,

Mwaura

et al. 2024

Molecules

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Prediction of the antibacterial activity of new chemical compounds is an important task, due to the growing problem of bacterial drug resistance. Generalized linear models (GLMs) were created using 85 amidrazone derivatives based on the results of antimicrobial activity tests, determined as the minimum inhibitory concentration (MIC) against Gram-positive bacteria: Staphylococcus aureus, Enterococcus faecalis, Micrococcus luteus, Nocardia corallina, and Mycobacterium smegmatis. For the analysis of compounds characterized by experimentally measured MIC values, we included physicochemical properties (e.g., molecular weight, number of hydrogen donors and acceptors, topological polar surface area, compound percentages of carbon, nitrogen, and oxygen, melting points, and lipophilicity) as potential predictors. The presence of R1 and R2 substituents, as well as interactions between melting temperature and R1 or R2 substituents, were also considered. The set of potential predictors also included possible biological effects (e.g., antibacterial, antituberculotic) of tested compounds calculated with the PASS (Prediction of Activity Spectra for Substances) program. Using GLMs with least absolute shrinkage and selection (LASSO), least-angle regression, and stepwise selection, statistically significant models with the optimal value of the adjusted determination coefficient and of seven fit criteria were chosen, e.g., Akaike’s information criterion. The most often selected variables were as follows: molecular weight, PASS_antieczematic, PASS_anti-inflam, squared melting temperature, PASS_antitumor, and experimental lipophilicity. Additionally, relevant to the bacterial strain, the interactions between melting temperature and R1 or R2 substituents were selected, indicating that the relationship between MIC and melting temperature depends on the type of R1 or R2 substituent.

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supporting

confidence: 93%

Modeling of Effectiveness of N3-Substituted Amidrazone Derivatives as Potential Agents against Gram-Positive Bacteria

Ćwiklińska-Jurkowska,

Paprocka,

Mwaura

et al. 2024

Molecules

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“…It is generally believed that drug molecules must be generally lipophilic to have good absorption [ 57 ]; however, the optimal lipophilicity for a drug-like molecule depends on the intended use and the target protein [ 58 ]. A compound that is too lipophilic may have poor solubility and bioavailability, while a compound that is too hydrophilic may have poor membrane permeability [ 59 ]. Lipophilicity exceeding five is often linked with undesired drug characteristics including limited water solubility, tissue accumulation, rapid metabolic turnover, and strong plasma protein binding [ 60 , 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

Unveiling the Potential of Ent-Kaurane Diterpenoids: Multifaceted Natural Products for Drug Discovery

Kibet,

Kimani,

Mwanza

et al. 2024

Pharmaceuticals

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Natural products hold immense potential for drug discovery, yet many remain unexplored in vast libraries and databases. In an attempt to fill this gap and meet the growing demand for effective drugs, this study delves into the promising world of ent-kaurane diterpenoids, a class of natural products with huge therapeutic potential. With a dataset of 570 ent-kaurane diterpenoids obtained from the literature, we conducted an in silico analysis, evaluating their physicochemical, pharmacokinetic, and toxicological properties with a focus on their therapeutic implications. Notably, these natural compounds exhibit drug-like properties, aligning closely with those of FDA-approved drugs, indicating a high potential for drug development. The ranges of the physicochemical parameters were as follows: molecular weights—288.47 to 626.82 g/mol; number of heavy atoms—21 to 44; the number of hydrogen bond donors and acceptors—0 to 8 and 1 to 11, respectively; the number of rotatable bonds—0 to 11; fraction Csp3—0.65 to 1; and TPSA—20.23 to 189.53 Å². Additionally, the majority of these molecules display favorable safety profiles, with only 0.70%, 1.40%, 0.70%, and 46.49% exhibiting mutagenic, tumorigenic, reproduction-enhancing, and irritant properties, respectively. Importantly, ent-kaurane diterpenoids exhibit promising biopharmaceutical properties. Their average lipophilicity is optimal for drug absorption, while over 99% are water-soluble, facilitating delivery. Further, 96.5% and 28.20% of these molecules exhibited intestinal and brain bioavailability, expanding their therapeutic reach. The predicted pharmacological activities of these compounds encompass a diverse range, including anticancer, immunosuppressant, chemoprotective, anti-hepatic, hepatoprotectant, anti-inflammation, antihyperthyroidism, and anti-hepatitis activities. This multi-targeted profile highlights ent-kaurane diterpenoids as highly promising candidates for further drug discovery endeavors.

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Alkaloids Isolated from Vepris glandulosa with Antidiabetic Properties: An In Vitro and In Silico Analysis

Ojuka,

Ochieng,

Ndarawit

et al. 2024

Chemistry & Biodiversity

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Diabetes is a major global health issue and as current treatments fail, the search for new antidiabetic drugs is crucial. This investigation, focusing on identifying potential antidiabetic compounds from the endangered plant species Vepris glandulosa, led to the isolation of two known alkaloids, choisyine acetate (1) and choisyine (2). The study established the in vitro inhibitory activities and in silico molecular interaction of the two alkaloids with α‐amylase based on IC50 values, Linewaever‐Burk/Dixon plot kinetic analyses and Molecular docking, respectively. The α‐amylase inhibition assay revealed noncompetitive inhibition for both compounds with IC50 and Ki values of 4.74±0.17 and 4.75 mM for compound 1, and 11.29±0.44 and 12.37 mM for compound 2, respectively. In comparison, the standard drug acarbose displayed a competitive mode of inhibition, with IC50 and Ki values of 11.99±0.02 and 12.68 mM, respectively. The binding affinities with α‐amylase were ‐6.42 and ‐6.07 kcal/mol for compounds 1 and 2, respectively relative to acarbose ‐8.03 Kcal/mol. Moreover, the predicted physicochemical and ADMET properties of these two compounds justified their potential as lead compounds for drug discovery. These compounds demonstrated remarkable inhibition potential comparable to the standard drug, highlighting their potential as viable alternatives in the management of diabetes.

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Assessment of Lipophilicity Parameters of Antimicrobial and Immunosuppressive Compounds

Cited by 7 publications

References 39 publications

Modeling of Effectiveness of N3-Substituted Amidrazone Derivatives as Potential Agents against Gram-Positive Bacteria

Modeling of Effectiveness of N3-Substituted Amidrazone Derivatives as Potential Agents against Gram-Positive Bacteria

Unveiling the Potential of Ent-Kaurane Diterpenoids: Multifaceted Natural Products for Drug Discovery

Alkaloids Isolated from Vepris glandulosa with Antidiabetic Properties: An In Vitro and In Silico Analysis

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