Cheminformatic Insight into the Differences between Terrestrial and Marine Originated Natural Products

Abstract

This is a new golden age for drug discovery based on natural products derived from both marine and terrestrial sources. Herein, a straightforward but important question is "what are the major structural differences between marine natural products (MNPs) and terrestrial natural products (TNPs)?" To answer this question, we analyzed the important physicochemical properties, structural features, and drug-likeness of the two types of natural products and discussed their differences from the perspective of evolution. In general, MNPs have lower solubility and are often larger than TNPs. On average, particularly from the perspective of unique fragments and scaffolds, MNPs usually possess more long chains and large rings, especially 8- to 10-membered rings. MNPs also have more nitrogen atoms and halogens, notably bromines, and fewer oxygen atoms, suggesting that MNPs may be synthesized by more diverse biosynthetic pathways than TNPs. Analysis of the frequently occurring Murcko frameworks in MNPs and TNPS also reveals a striking difference between MNPs and TNPs. The scaffolds of the former tend to be longer and often contain ester bonds connected to 10-membered rings, while the scaffolds of the latter tend to be shorter and often bear more stable ring systems and bond types. Besides, the prediction from the naïve Bayesian drug-likeness classification model suggests that most compounds in MNPs and TNPs are drug-like, although MNPs are slightly more drug-like than TNPs. We believe that MNPs and TNPs with novel drug-like scaffolds have great potential to be drug leads or drug candidates in drug discovery campaigns.

Computational Approaches to Identify Natural Products as Inhibitors of DNA Methyltransferases

“…purely synthetic organic molecules is, overall, the feasibility of the former to exert a biological activity and increased chemical diversity [11]. The chemical space of natural products is vast, and its molecular diversity has been quantified in several studies over the years [37][38][39][40][41]. A major contribution to these studies has been the increasing availability of natural products collections in the public domain [42].…”

“…The large importance of natural products in drug discovery has boosted the development of open access applications to mine these rich repositories. Few examples are ChemGPS-NP, TCMAnalyzer and other resources described elsewhere[46][47][48][49].The chemical space of natural products from different sources has been compared to several other collections including the chemical space of drugs approved for clinical use and synthetic compounds[37][38][39][40][41]. These studies revels that certainly the chemical space of natural products is vast;there is a notable overlap with the chemical space of drugs but also natural products cover novelregions of the chemical space.…”

Natural Products of Marine Macroalgae from South Eastern Australia, with Emphasis on the Port Phillip Bay and Heads Regions of Victoria

“…Many of these compounds displayed very promising biological activity, making them serious contenders as anti-cancer and anti-bacterial drugs or drug leads. A recent cheminformatics study has highlighted the potential of MNPs to produce drug-like chemical compounds [4]. Despite this, MNPs remain less studied than TNPs, mostly due to the relative ease with which TNP specimens can be obtained and cultivated.…”

“…Currently, there are 10 FDA-approved marine-derived pharmaceutical drugs, together with 30 potential candidates for application in a number of disease areas that are in different stages of clinical trials (Phase I, II and III) Figure 1 [5]. potential of MNPs to produce drug-like chemical compounds [4]. Despite this, MNPs remain less studied than TNPs, mostly due to the relative ease with which TNP specimens can be obtained and cultivated.…”

Free Marine Natural Products Databases for Biotechnology and Bioengineering

“…[16][17][18][19][20][21][22][23] Furthermore, the chemical differences between marine and terrestrial natural compounds have been assessed, clarifying the importance of assembling available data for current known marine compounds due to their overall peculiar and unique characteristics when compared to terrestrial ones. [24] The availability of free-access chemical databases of MNPs should prompt and accelerate putative applications for a myriad of marine origin compounds. Data could be applied not only to the discovery of new bioactive compounds but also to new materials and high-value molecules, e.g., pigments from microalgae.…”