Mar.Drugs 2014,12 1073 Additionally,the synthesis or hemisynthesis of a bioactive natural compound must be supported by a correct identification of the compound isolated from the biological source.Despite the fact that modern methodologies of struetural elucidation are well advanced,errors can never be completely ruled out.In fact,there are numerous structural revisions reported in literature,even of recently elucidated NP.In average,per 5-year period,369 NP and 135 MNP are misassigned [58].The structural complexity of the isolated compounds and the small amount of samples,especially in the case of compounds from marine sources.can contribute to misassignments which can be divided in several categories:incorrect formula,constitution (planar connectivity),double bond configuration, absolute configuration,and one or several stereocenters assigned incorrectly [59]. To avoid"rediscovery of the known"more specialized and effective dereplication strategies need to be employed.With over 150,000 small molecules characterized from natural sources,previously known natural compounds are often re-isolated during bioassay-guided fractionation and that should be avoided [29].Hyphenated technics such as liquid chromatography with ultraviolet detection (LC-UV),liquid chromatography-mass spectrometry (LC-MS,LC-MS/MS)or LC-NMR are valuable toos for the dereplication process,especially if used early in the prefractionation step [60].Access to suitable databases is essential for the rapid dereplication of crude extracts in natural product research. Several commercial databases are available to implement the dereplication process,from which the most comprehensive ones are:Chemical abstracts,including NAPRALERT,Beilstein,AntiBase [61] (>40,000 natural compounds from micro-organisms and higher fungi),MarinLit (-24,000 marine compounds isolated from approximately 6000 species)[62]Chapman&Hall's Dictionary of Natural Products (~170.000 compounds from both marine and terrestrial organisms)63]and NAPROC-13 ('CNMR spectral information of over 6000 natural compounds)[641. When using pure natural compound libraries,virtual screening is also a possibility that must be stressed out.Virtual screening can be used for browsing databases in the quest for molecules fitting either an established pharmacophore model or a three dimensional structure of a macromolecular target.The advantages of this approach overinro sereening are obvious:higher capacity,no need for physically isolating the compounds,less time-consuming and expensive and theoretically interactions of all compounds to all structurally defined targets can be calculated and predicted Additionally early evaluation of absorption.distribution.metabolism.and excretion/toxicity in pharmacokinetics(ADMET)properties is also possible [65].But,because virtual screening is only a predictive tool,in the case of NP it is important the integration with traditional avenues,gathering information from bioassay guided fractionation,on-line analytical activity an optimization of drug lead discovery 65. Finally.upon the identification of a lead it is necessary to understand its mode of action against the specific target.This includes secondary testing in which molecular and cellular techniques are normally applied.This identification constitutes a major challenge but is becoming more and more compulsory in both pharmaceutical and cosmeceutical industriesMar. Drugs 2014, 12 1073 Additionally, the synthesis or hemisynthesis of a bioactive natural compound must be supported by a correct identification of the compound isolated from the biological source. Despite the fact that modern methodologies of structural elucidation are well advanced, errors can never be completely ruled out. In fact, there are numerous structural revisions reported in literature, even of recently elucidated NP. In average, per 5-year period, 369 NP and 135 MNP are misassigned [58]. The structural complexity of the isolated compounds and the small amount of samples, especially in the case of compounds from marine sources, can contribute to misassignments which can be divided in several categories: incorrect formula, constitution (planar connectivity), double bond configuration, absolute configuration, and one or several stereocenters assigned incorrectly [59]. To avoid ―rediscovery of the known‖ more specialized and effective dereplication strategies need to be employed. With over 150,000 small molecules characterized from natural sources, previously known natural compounds are often re-isolated during bioassay-guided fractionation and that should be avoided [29]. Hyphenated technics such as liquid chromatography with ultraviolet detection (LC-UV), liquid chromatography-mass spectrometry (LC-MS, LC-MS/MS) or LC-NMR are valuable tools for the dereplication process, especially if used early in the prefractionation step [60]. Access to suitable databases is essential for the rapid dereplication of crude extracts in natural product research. Several commercial databases are available to implement the dereplication process, from which the most comprehensive ones are: Chemical abstracts, including NAPRALERT, Beilstein, AntiBase [61] (>40,000 natural compounds from micro-organisms and higher fungi), MarinLit (~24,000 marine compounds isolated from approximately 6000 species) [62], Chapman & Hall‘s Dictionary of Natural Products (~170,000 compounds from both marine and terrestrial organisms) [63] and NAPROC-13 ( 13CNMR spectral information of over 6000 natural compounds) [64]. When using pure natural compound libraries, virtual screening is also a possibility that must be stressed out. Virtual screening can be used for browsing databases in the quest for molecules fitting either an established pharmacophore model or a three dimensional structure of a macromolecular target. The advantages of this approach over in vitro screening are obvious: higher capacity, no need for physically isolating the compounds, less time-consuming and expensive and theoretically, interactions of all compounds to all structurally defined targets can be calculated and predicted. Additionally early evaluation of absorption, distribution, metabolism, and excretion/toxicity in pharmacokinetics (ADMET) properties is also possible [65]. But, because virtual screening is only a predictive tool, in the case of NP it is important the integration of in silico screening with traditional avenues, gathering information from bioassay guided fractionation, on-line analytical activity profiling, ethnopharmacological screening, if it is the case, and chemoinformatics, in order to achieve an optimization of drug lead discovery [65]. Finally, upon the identification of a lead it is necessary to understand its mode of action against the specific target. This includes secondary testing in which molecular and cellular techniques are normally applied. This identification constitutes a major challenge but is becoming more and more compulsory in both pharmaceutical and cosmeceutical industries