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dc.contributor.authorKazan, Hilal
dc.contributor.authorYılancıoğlu, Kaan
dc.contributor.authorWeinstein, Zohar B.
dc.contributor.authorMeydan, Cem
dc.contributor.authorAkhmetov, Azat
dc.contributor.authorToprak, Işıl
dc.contributor.authorDurmaz, Arda
dc.contributor.authorIossifov, Ivan
dc.contributor.authorRoth, Frederick P.
dc.contributor.authorÇokol, Murat
dc.date.accessioned2019-12-25T06:34:11Z
dc.date.available2019-12-25T06:34:11Z
dc.date.issued2014
dc.identifier.citationKazan H., Yılancıoğlu, K., Weinstein, Z. B., Meydan, C., Akhmetov, A., Toprak, I., Durmaz, A., Roth, F. P., Iossifov, I., Çokol, M. (2014). Target Independent Prediction of Drug Synergies Using Only Drug Lipophilicity. Journal of Chemical Information and Modeling, 54(8), 2286–2293.en_US
dc.identifier.issn1549-9596
dc.identifier.urihttp://hdl.handle.net/20.500.12566/178
dc.description.abstractPhysicochemical properties of compounds have been instrumental in selecting lead compounds with increased drug-likeness. However, the relationship between physicochemical properties of constituent drugs and the tendency to exhibit drug interaction has not been systematically studied. We assembled physicochemical descriptors for a set of antifungal compounds (“drugs”) previously examined for interaction. Analyzing the relationship between molecular weight, lipophilicity, H-bond donor, and H-bond acceptor values for drugs and their propensity to show pairwise antifungal drug synergy, we found that combinations of two lipophilic drugs had a greater tendency to show drug synergy. We developed a more refined decision tree model that successfully predicted drug synergy in stringent cross-validation tests based on only lipophilicity of drugs. Our predictions achieved a precision of 63% and allowed successful prediction for 58% of synergistic drug pairs, suggesting that this phenomenon can extend our understanding for a substantial fraction of synergistic drug interactions. We also generated and analyzed a large-scale synergistic human toxicity network, in which we observed that combinations of lipophilic compounds show a tendency for increased toxicity. Thus, lipophilicity, a simple and easily determined molecular descriptor, is a powerful predictor of drug synergy. It is well established that lipophilic compounds (i) are promiscuous, having many targets in the cell, and (ii) often penetrate into the cell via the cellular membrane by passive diffusion. We discuss the positive relationship between drug lipophilicity and drug synergy in the context of potential drug synergy mechanisms.en_US
dc.description.sponsorshipNo sponsoren_US
dc.language.isoengen_US
dc.publisherJournal of Chemical Information and Modelingen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAntimicrobial agentsen_US
dc.subjectAntimikrobiyal ajanlartr_TR
dc.subjectToxicological synergyen_US
dc.subjectToksikolojik sinerjitr_TR
dc.subjectFungien_US
dc.subjectMantarlartr_TR
dc.subjectDrug synergyen_US
dc.subjectİlaç sinerjisitr_TR
dc.subjectToxicityen_US
dc.subjectToksisitetr_TR
dc.titleTarget-independent prediction of drug synergies using only drug lipophilicityen_US
dc.typeinfo:eu-repo/semantics/articleen_US
dc.relation.publicationcategoryInternational publicationen_US
dc.identifier.wosWOS:000340861900011
dc.identifier.scopus2-s2.0-84906543224
dc.identifier.volume54
dc.identifier.issue8
dc.identifier.startpage2286
eperson.identifier.endpage2293
dc.contributor.orcid0000-0003-2461-4579 [Kazan, Hilal]
dc.contributor.abuauthorKazan, Hilal
dc.contributor.yokid107780 [Kazan, Hilal]
dc.contributor.ScopusAuthorID35094213400 [Kazan, Hilal]
dc.identifier.PubMedID25026390
dc.identifier.doihttps://doi.org/10.1021/ci500276x


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