Analysis of the Acid/Base Profile of Natural Products from Different Sources

Abstract

For many years drug discovery and other areas in chemistry have successfully relied on natural products. Recent advances in computational methods have made possible to study the chemical space of natural products from different sources. Ionizable acidic and basic functional groups heavily influence physicochemical properties and thus a molecule's absorption, distribution, metabolism, excretion, and toxicity characteristics as well as their affinity for biological targets. This work reports the generation and critical comparison of the acid/base profiles of ten chemical databases including seven natural products sets from different origins, a set of semisynthetic compounds, a collection of approved drugs, and a compendium of food chemicals. Similarities were found in the proportion of the main charge state categories among the natural products databases with few differences in their pKa distributions. Clear differences were observed between natural products and the approved drugs and semi‐synthetic natural products databases, whereas natural products share some trends with the food chemical database. We noted that the natural products collections comprise around 45 % of neutral compounds. The proportion of single acids was approximately twice that found for FDA drugs, and they demonstrated a similar distribution of pKa values. In contrast to drugs, only 5 % of compounds among the natural products sets had a single basic group. Likewise, simple ampholytes were less prevalent in the natural products databases relative to drugs.

The Acid/Base Characterization of Molecules with Epigenetic Activity

“…Figure 2B shows the p K a distribution of the single bases of the active and inactive epigenomics compounds along with the reference sets. As observed in previous studies, the drugs and natural products in UNPD have mostly strong bases with a high incidence of amines [36] . On the other hand, there are subtle differences in the basic p K a distributions of the epigenetic ligands (active and inactive) and the food chemicals, but the three collections have around 60 % of bases with p K a values below 4.…”

“…As reported before, the acid/base profile of food chemicals was highly similar to the natural products, and these two are different from the approved drugs [36] . Despite this, all the reference datasets showed equivalent proportions of single acids which were also similar to the proportion of single acids observed in the Epidatabase.…”

“…This classification considered varying pH conditions encountered in the human body and, consequently, of interest to drug development. The eight groups implemented in the current workflow of KNIME coincide with the classification groups of previous acid/base profiling of compound datasets and help make cross‐comparison with published studies [28,34–36] . The compounds were organized as “always ionized” when at least one of their acidic functional groups had an estimated p K a value below 0, or at least one of their basic functional groups had an estimated p K a value above 12.…”

Characteristics of Biopeptides Released In Silico from Collagens Using Quantitative Parameters

“…Such properties also refer to bioactive food components, like peptides. Comparison of various properties of drugs and food components has recently become the focus of the scientific interests [ 82 , 83 , 84 ]. ADMET calculation would significantly aid the in silico evaluation of the potential bioactivity of peptides.…”

Progress on open chemoinformatic tools for expanding and exploring the chemical space

“…Recently the in silico acid-based profile of small molecules has been used to explore the chemical space of small molecules with epigenetic activity [ 27 ] and natural products from different sources [ 28 ].…”