The impact of aromatic ring count on the bioavailability of chemical compounds.
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Date
2019
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Abstract
Aromatic rings are a negative contributing factor in the bioavailability of chemical compounds in drug discovery. Due to the inevitable effect the aromatic rings possess on the bioavailability of chemical compounds, methods to continuously evaluate their effect should be ceaseless. As such, this study aimed at investigating the impact of aromatic ring count on the bioavailability of chemical compounds by screening a small collection compound library comprising 13 compounds. The permeability of chemical compounds was evaluated using the PAMPA assay; the results further analysed through spectrophotometry. The PAMPA assay is an automated system and was used to allow for rapid screening of compounds and the screening was successful. Overall, only four chemical compounds showed poor permeability: ammonium bromide, gibberellic acid, salicylic acid, and PMSF. Osiris Property Explorer was used to screen all 13 compounds for cLogP, LogS, TPSA, Toxicity risks, drug-likeness and drug score. Most of these compounds produced suitable logP (< 5) and were therefore predicted to possess good absorption and permeability properties. Percentage protein binding was assessed separately; all chemical compounds were screened for percentage protein binding using Amicon Ultra-15 Centrifugal Filter method. The results indicated a broad range of protein binding for all chemical compounds tested (70.29 – 98.23%). Lipinski’s Rule of Five was applied to all chemical compounds and compounds were scored against the four rules. Most compounds adhered to all four rules with only two compounds violating one or two rules. A relationship between parameters: permeability, drug-score, and percentage protein binding, against the aromatic ring count of chemical compounds, was explored. Overall, no real relationship existed between any of these parameters and aromatic ring count, as was indicated by low correlation coefficients (R2) (< 0.95). Overall, this study resulted in the successful screening of 13 chemical compounds and the establishment of effective permeability, percentage protein binding assays for future studies.
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Masters Degree. University of KwaZulu-Natal, Pietermaritzburg.