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Pregled bibliografske jedinice broj: 563816

Časopis

Autori: Stepanić, Višnja; Žiher, Dinko; Gabelica-Marković, Vesna; Jelić, Dubravko; Nunhuck, Shenaz; Valko, Klara; Koštrun, Sanja
Naslov: Physicochemical profile of macrolides and their comparison with small molecules
( Physicochemical profile of macrolides and their comparison with small molecules )
Izvornik: European journal of medicinal chemistry (0223-5234) 47 (2012); 462-472
Vrsta rada: članak
Ključne riječi: drug-likeness; high-throughput screening; lipopilicity; macrolides; physicochemical property
( drug-likeness; high-throughput screening; lipopilicity; macrolides; physicochemical property )
Sažetak:
Macrolides are stereospecific macrolactones of high molecular weights. Herein, 600 mostly semisynthetic macrolides are compared with 50, 000 small non-macrolide synthetic molecules in terms of measured physicochemical properties in order to assess the drug-likeness and developability chances of macrolides. The pre-selected set of diverse macrolides is comprised mostly of derivatives of clarithromycin and azithromycin cores. Lipophilicity (CHI logD), affinity for immobilized artificial membranes (CHI IAM), human serum albumin (HSA) and α1-acid glycoprotein (AGP) plasma protein bindings (PPB), DMSO precipitative solubility as well as artificial membrane permeability (AMP) have been determined by high-throughput screening methods. It has been found that macrolides and small molecules have similar lipophilicity profiles, though macrolides show weaker PPB and have better solubility than small discovery molecules. However, macrolides are poorly permeable and have high affinity for immobilized artificial membranes signifying their strong interaction with biological phospholipids. In order to retain the drug-like profile, the design of novel macrolide molecules should be focused on optimisation of macrolide cores, that is macrolactone moiety with sugars and other small substituents avoiding large substituents and flexible linkers such as in conjugate derivatives.
Projekt / tema: 098-0982464-2511
Izvorni jezik: eng
Rad je indeksiran u
bazama podataka:
Current Contents Connect (CCC)
MEDLINE
Scopus
SCI-EXP, SSCI i/ili A&HCI
Science Citation Index Expanded (SCI-EXP) (sastavni dio Web of Science Core Collectiona)
Kategorija: Znanstveni
Znanstvena područja:
Kemija,Temeljne medicinske znanosti,Farmacija
URL Internet adrese: http://dx.doi.org/10.1016/j.ejmech.2011.11.016
http://www.sciencedirect.com/science/article/pii/S0223523411008385
http://ac.els-cdn.com/S0223523411008385/1-s2.0-S0223523411008385-main.pdf?_tid=4e9aa02a-a757-11e2-8194-00000aab0f6b&acdnat=1366200599_5d243843a949cb9f949ea10fdbe61551
Broj citata:
Altmetric:
DOI: 10.1016/j.ejmech.2011.11.016
URL cjelovitog teksta: http://dx.doi.org/10.1016/j.ejmech.2011.11.016
Google Scholar: Physicochemical profile of macrolides and their comparison with small molecules
Upisao u CROSBI: stepanic@irb.hr (stepanic@irb.hr), 6. Pro. 2011. u 08:00 sati



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