We discuss further details on the concepts of “drug-likeness”, “lead-likeness”, and “natural product-likeness”. The discussion will first focus on natural products as drugs, then a discussion of previous studies in which the complexities of the scaffolds and chemical space of naturally occurring compounds have been compared with synthetic, semi-synthetic compounds and FDA-approved drugs. This is followed by guiding principles for designing “drug-like” natural product libraries for lead compound discovery purposes. We end up by presenting a tool for measuring “natural product-likeness” of compounds and a brief presentation of machine learning approaches and a binary quantitative structure-activity relationship (QSAR) for classifying drugs from non-drugs and natural compounds from non-natural ones, respectively.

Fungal infections caused by Candida spp. are responsible for high hospital morbidity and mortality rates. Therefore, there is a continuous search for new antifungal medicines, particularly ones with anti-Candida activity. This review analyzed articles published between 2002 and 2023 considering the anti-Candida activity of chemical compounds identified or isolated in plants of the Anacardiaceae family. In addition, the in-silico prediction of the isolated compounds described was performed. The analysis of 35 studies showed that extracts, essential oils, and compounds from the anti-Candida activity were frequently determined in vitro using the minimum inhibitory concentration (MIC). The most commonly tested species were Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii, respectively. Essential oils were the most used form (37% of the studies). The isolated compounds with antifungal effects include cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-o-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, and oleanolic aldehyde. The in-silico evaluation of those isolated compounds revealed the compounds' drug-likeness and possible antifungal activity. However, some of them showed high toxicity. In conclusion, compounds from the Anacardiaceae family show promise for developing new therapeutic antifungal drugs, especially in combination with conventional antifungals.

Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder. One of the important therapeutic approaches of AD is the inhibition of β‐site APP cleaving enzyme‐1 (BACE1). This enzyme plays a central role in the synthesis of the pathogenic β-amyloid peptides (Aβ) in Alzheimer's disease. A group of potent BACE1 inhibitors with known x-ray structures (PDB ID 5i3X, 5i3Y, 5iE1, 5i3V, 5i3W, 4LC7, 3TPP) were studied by molecular dynamics simulation and binding energy calculation employing MM_GB(PB)SA. The calculated binding energies gave Kd values 0.139 µM, 1.39 nM, 4.39 mM, 24.3 nM, 1.39 mM, 29.13 mM and 193.07 nM, respectively. These inhibitors showed potent inhibitory activities in enzymatic and cell assays. The Kd values were compared with experimental values, the structures were discussed in view of the energy contributions to binding. Drug likeness of these inhibitors is also discussed. Accommodation of ligands in the catalytic site of BACE1 is discussed depending on the type of fragment involved in each structure. Molecular dynamics (MD) simulations and energy studies were used to explore the recognition of the selected BACE1 inhibitors by Asp 32, Asp228 and the hydrophobic flap. The results show that selective BACE1 inhibition may be due to the formation of strong electrostatic interactions with Asp32 and Asp228 and a large number of hydrogen bonds, π-π and Van der Waals interactions with the amino acid residues located inside the catalytic cavity. Interactions with the ligands show a similar binding mode with BACE1. These results help to rationalize the design of selective BACE1 inhibitors.

Big data is considered to be the solution to many complex problems, but its application appears to be relegated to the problems that are factorable (e.g., the tensor-like operations which reflect separable elements), not the non-factorable data from teamwork, team intelligence, and possibly not individual consciousness. In contrast, the quantum likeness of interdependence is set apart from the standard science of teams by recognizing a measurement problem between a team and its individual teammates, and between individual beliefs and actions. Teams that concern us are based on artificial intelligence (AI) and machine learning (ML) systems, which we find lacking for two reasons. First, neither AI nor ML models the human's timeless need for debate to solve a problem at the social level when facing uncertainty or complexity, where the debate of proposed actions serves to establish the boundaries of a problem in reality, no matter how complex nor uncertain. Second, at the individual level exists the illusion of a unified reality propagated by a bifurcated brain that we assume is split to determine a context with narrative and bounded spaces. We hypothesize that the quantum-likeness of interdependence applied to autonomous human-machine teams suggests that at the social level, debate models an individual's bifurcated brain, providing advantages for human-machine teams in freer systems over those oppressed by command and control systems (e.g., authoritarian regimes). Human-machine teams are coming, but they are not yet available, forcing us to rely on data from human systems. We close with plans for future research.

We study two fundamental linguistic channels ‒ the Sentences and the Interpunctions channels ‒ and show they can reveal deeper connections between texts. The theory applied does not follow the actual paradigm of linguistic studies. As study‒case, we consider the Greek New Testament, with the purpose of determining mathematical connections between its texts and possible differences in writing style (mathematically defined) of writers, and in reading skill required to their readers. The analysis is based on deep‒language parameters and communication/information theory. To set the New Testament texts in the larger Greek Classical Literature, we consider texts written by Aesop, Polybius, Flavius Josephus and Plutarch. The results largely confirm what scholars have found about the New Testament texts giving, therefore, credibility to the theory. The gospel according to John is very similar to Fables written by Aesop. Surprisingly, the Epistle to the Hebrews and Apocalypse, are each other “photocopy” in the two linguistic channels, and not linked to all other texts. These two texts deserve further study by historians of the early Christian Church Literature at the level of meaning, readers and possible Old Testament texts which might have influenced them. The theory can guide scholars to study any literary corpus.