The Chemical Property Position of Bedaquiline Construed by a Chemical Global Positioning System-Natural Product

Alajlani, Muaaz Mutaz (author): Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala Univ, Fac Pharm, BMC Biomed Ctr, Dept Pharmaceut Biosci,Pharmacognosy, S-75123 Uppsala, Sweden.;Univ Halle Wittenberg, Inst Pharm, Dept Pharmaceut Biol Pharmacognosy, D-06120 Halle, Germany.;Qasyoun Private Univ, Fac Pharm, Main Campus, Damascus Build 131, Syria.

(creator_code:org_t)

Related links:: https://doi.org/10.3...; show more...; https://uu.diva-port... (primary) (Raw object); https://www.mdpi.com...; https://urn.kb.se/re...; https://doi.org/10.3...; show less...

Abstract Subject headings

Bedaquiline is a novel adenosine triphosphate synthase inhibitor anti-tuberculosis drug. Bedaquiline belongs to the class of diarylquinolines, which are antituberculosis drugs that are quite different mechanistically from quinolines and flouroquinolines. The fact that relatively similar chemical drugs produce different mechanisms of action is still not widely understood. To enhance discrimination in favor of bedaquiline, a new approach using eight-score principal component analysis (PCA), provided by a ChemGPS-NP model, is proposed. PCA scores were calculated based on 35 + 1 different physicochemical properties and demonstrated clear differences when compared with other quinolines. The ChemGPS-NP model provided an exceptional 100 compounds nearest to bedaquiline from antituberculosis screening sets (with a cumulative Euclidian distance of 196.83), compared with the different 2Dsimilarity provided by Tanimoto methods (extended connective fingerprints and the Molecular ACCess System, showing 30% and 182% increases in cumulative Euclidian distance, respectively). Potentially similar compounds from publicly available antituberculosis compounds and Maybridge sets, based on bedaquiline's eight-dimensional similarity and different filtrations, were identified too.

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmaceutical S ...

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