In silico approaches to prediction of aqueous and DMSO solubility of drug-like compounds: trends, problems and solutions.
The solubility of drugs and drug-like compounds has been the subject of extensive studies aimed at finding a way to predict solubility from molecular structure. The aqueous solubility of a drug is an important factor that influences its absorption, distribution and elimination in the body. Poor aqueous solubility often causes a drug to appear inactive and may cause other biological problems. Compound solubility in DMSO represents another serious problem in early stages of drug discovery. An appreciation of the factors affecting a compound's DMSO solubility could help in predicting the storage conditions and appropriateness of compounds for primary bioscreening programs. In silico procedures for estimation of water and DMSO solubility represent extremely useful tools for the drug discovery practitioners. In this review, we provide a critical discussion of in silico models for the prediction of DMSO and water solubility of drug-like compounds used for virtual screening. We describe the main tendencies in the field, "booming" approaches and unsolved problems. A critical analysis of the accuracy and applicability of methods is provided.
Biomedical Department, Institute of Bioorganic & Petrochemistry, Murmanskaya 1, 02094 Kyiv, Ukraine.
Konstantin V
KV
Balakin
Nikolay P
NP
Savchuk
Igor V
IV
Tetko
D001682:Biological Availability; D020650:Combinatorial Chemistry Techniques; D003198:Computer Simulation; D004121:Dimethyl Sulfoxide / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry*
D004364:Pharmaceutical Preparations; D014867:Water; D004121:Dimethyl Sulfoxide