title: Assessing the drug-likeness of lamellarins, a marine-derived natural product class with diverse oncological activities.
abstract: Natural products currently represent an underutilized source of leads for the pharmaceutical industry, especially when one considers that almost 50% of all drugs were either derived from such sources or are very closely related. Lamellarins are a class of natural products with diverse biological activities and have entered into preclinical development for the treatment of multidrug-resistant tumors. Although these compounds demonstrated good cell penetration, as observed by their low microM activity in whole cell models, they have not been extensively profiled from a physicochemical point of view, and this is the goal of this study. For this study, we have determined the experimental logP values of a set of 25 lamellarins, given it is the single most important parameter in determining multiple ADMET parameters. We also discuss the relationship between this natural product class, natural product derivatives in development and on the market, oral marketed drugs, as well as drug molecules in development, using a range of physicochemical parameters in conjunction with principal components analysis (PCA). The impact of this systematic analysis on our ongoing medicinal chemistry strategy is also discussed.
authors.affiliation: Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Moo 4, Vibhavadee-Rangsit Highway, Laksi, Bangkok 10210, Thailand. montakarn@cri.or.th
authors.forename: Montakarn
authors.initials: M
authors.lastname: Chittchang
authors.forename: M Paul
authors.initials: MP
authors.lastname: Gleeson
authors.forename: Poonsakdi
authors.initials: P
authors.lastname: Ploypradith
authors.forename: Somsak
authors.initials: S
authors.lastname: Ruchirawat
mesh_terms: D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D001688:Biological Products / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D055598:Chemical Phenomena; D019295:Computational Biology; D055808:Drug Discovery; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D007753:Laboratories; D009792:Oceans and Seas; D025341:Principal Component Analysis; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D006576:Heterocyclic Compounds, 4 or More Rings