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Marine toxins, produced by various marine microorganisms, pose significant risks to both marine ecosystems and human health. Understanding their diverse structures and properties is crucial for effective mitigation and exploration of their potential as therapeutic agents. This study presents a comparative analysis of two hydrophilic and two lipophilic marine toxins, examining their reactivity properties and bioavailability scores. By investigating similarities among these structurally diverse toxins, valuable insights into their potential as precursors for novel drug development can be gained. The exploration of lipophilic and hydrophilic properties in drug design is essential due to their distinct implications on drug distribution, elimination, and target interaction. By elucidating shared molecular properties among toxins, this research aims to identify patterns and trends that may guide future drug discovery efforts and contribute to the field of molecular toxinology. The findings from this study have the potential to expand knowledge on toxins, facilitate a deeper understanding of their bioactivities, and unlock new therapeutic possibilities to address unmet biomedical needs. The results showcased similarities among the studied systems, while also highlighting the exceptional attributes of Domoic Acid (DA) in terms of its interaction capabilities and stability.

Abstract Cladosporium spp. have been reported for their great diversity of secondary metabolites which represent as a prominent base material for verifying the biological activities. Several bioactive compounds which have antimicrobial, cytotoxic, quorum sensing inhibitory and phytotoxic activities have been isolated from Cladosporium species. Most of them are still needed to be explored for their anticancer properties. Therefore, the present study is focused on screening and identifying the bioactive compounds of Cladosporium spp. for their anticancer activity via the integrated approaches of Molecular Docking (MD), Molecular Dynamics Simulation (MDS) and Density Functional Theory (DFT) studies. A total of 123 bioactive compounds of Cladosporium spp. were explored for their binding affinity with the selected breast cancer drug target receptor such as estrogen receptor alpha (PDB:6CBZ). The Molecular Docking studies revealed that amongst the bioactive compounds screened, Altertoxin X and Cladosporol H showed a good binding affinity of − 10.5 kcal/mol and − 10.3 kcal/mol, respectively, with the estrogen receptor alpha when compared to the reference compound (17 $$\upbeta$$ β -Estradiol: − 10.2 kcal/mol). The MDS study indicated the stable binding patterns and conformation of the estrogen receptor alpha-Altertoxin X complex in a stimulating environment. In addition, in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) study suggested that Altertoxin X has a good oral bioavailability with a high LD $$_{50}$$ 50 value of 2.375 mol/kg and did not cause any hepatotoxicity and skin sensitization. In summary, the integrated approaches revealed that Altertoxin X possesses a promising anticancer activity and could serve as a new therapeutic drug for breast cancer treatment.

This work highlights the significant potential of marine toxins, particularly saxitoxin (STX) and its derivatives, in the exploration of novel pharmaceuticals. These toxins, produced by aquatic microorganisms and collected by bivalve mollusks and other filter-feeding organisms, offer a vast reservoir of chemical and biological diversity. They interact with sodium channels in physiological processes, affecting various functions in organisms. Exposure to these toxins can lead to symptoms ranging from tingling sensations to respiratory failure and cardiovascular shock, with STX being one of the most potent. The structural diversity of STX derivatives, categorized into carbamate, N-sulfocarbamoyl, decarbamoyl, and deoxydecarbamoyl toxins, offers potential for drug development. The research described in this work aimed to computationally characterize 18 STX derivatives, exploring their reactivity properties within marine sponges using conceptual density functional theory (CDFT) techniques. Additionally, their pharmacokinetic properties, bioavailability, and drug-likeness scores were assessed. The outcomes of this research were the chemical reactivity parameters calculated via CDFT as well as the estimated pharmacokinetic and ADME properties derived using computational tools. While they may not align directly, the integration of these distinct datasets enriches our comprehensive understanding of the compound’s properties and potential applications. Thus, this study holds promise for uncovering new pharmaceutical candidates from the considered marine toxins.

Abstract Aspergillipeptide D is a cyclic pentapeptide isolated from the marine gorgonian Melitodes squamata-derived fungus Aspergillus sp. SCSIO 41501 that it has been shown to present moderate activity against herpes virus simplex type 1 (HSV-1). Thus, this paper presents the results of a computational study of this cyclopentapeptide’s chemical reactivity and bioactivity properties using a CDFT-based computational peptidology (CDFT-CP) methodology, which is derived from combining chemical reactivity descriptors derived from Conceptual Density Functional Theory (CDFT) and some Cheminformatics tools which may be used. This results in an improvement of the virtual screening procedure by a similarity search allowing the identification and validation of the known ability of the peptide to act as a possible useful drug. This was followed by an examination of the drug’s bioactivity and pharmacokinetics indices in relation to the ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) characteristics. The findings provide further evidence of the MN12SX density functional’s superiority in proving the Janak and Ionization Energy theorems using the proposed KID approach. This has proven to be beneficial in accurately predicting CDFT reactivity characteristics, which aid in the understanding of chemical reactivity. The Computational Pharmacokinetics study revealed the potential ability of Aspergillipeptide D as a therapeutic drug through the interaction with different target receptors. The ADMET indices confirm this assertion through the absence of toxicity and good absorption and distribution properties.

For many years, the primary focus has been on finding effective treatments for Alzheimer’s disease (AD), which has led to the identification of promising therapeutic targets. The necessity for AD stage-dependent optimal settings necessitated a herbal therapy strategy. The plant species Areca Catechu L. (AC) was selected based on the traditional uses against CNS-related diseases. AC leaf extract were prepared using a Soxhlet extraction method and hydroxyapatite nanoparticles (HAp-NPs) were synthesized from the same (AC-HAp-NPs). Powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED) and fourier transform infrared spectroscopy (FTIR) were used to confirm the structure and morphology of the as-prepared AC-HAp-NPs. The crystalline character of the AC-HAp-NPs was visible in the XRD pattern. The synthesized material was found to be nanoflake, with an average diameter of 15–20 nm, according to SEM analysis. The TEM and SAED pictures also revealed the form and size of AC-HAp-NPs. In vitro anti-acetylcholinesterase and butyrylcholinesterase (AChE and BChE) activities of hydroxyapatite nanoparticles produced from an AC leaf extract was tested in this study. When compared to control, AC-HAp-NPs had higher anti-AChE and BChE activity. The anti-acetylcholinesterase action of phytoconstituents generated from AC leaf extract was mediated by 4AQD and 4EY7, according to a mechanistic study conducted utilizing in silico research. The global and local descriptors, which are the underpinnings of Conceptual Density Functional Theory (CDFT), have been predicted through the MN12SX/Def2TZVP/H2O model chemistry to help in the comprehension of the chemical reactivity properties of the five ligands considered in this study. The CDFT experiments are supplemented by the calculation of several useful calculated pharmacokinetics indices, their expected biological targets connected to the bioavailability of the five ligands in order to further the goal of studying their bioactivity.

Stellatolides are natural compounds that have shown promising biological activities, including antitumor, antimicrobial, and anti-inflammatory properties, making them potential candidates for drug development. Chemical Reactivity Theory (CRT) is a branch of chemistry that explains and predicts the behavior of chemical reactions based on the electronic structure of molecules. Conceptual Density Functional Theory (CDFT) and Computational Peptidology (CP) are computational approaches used to study the behavior of atoms, molecules, and peptides. In this study, we present the results of our investigation of the chemical reactivity and ADMET properties of Stellatolides A-H using a novel computational approach called Conceptual DFT-based Computational Peptidology (CDFT-CP). Our study uses CDFT and CP to predict the reactivity and stability of molecules and to understand the behavior of peptides at the molecular level. We also predict the ADMET properties of the Stellatolides A–H to provide insight into their effectiveness, potential side effects, and optimal dosage and route of administration, as well as their biological targets. This study sheds light on the potential of Stellatolides A–H as promising candidates for drug development and highlights the potential of CDFT-CP for the study of other natural compounds and peptides.

A new copper(I) complex, [Cu2(L)2dppm](PF6)2 (1) [L = 3-(2-Pyridyl)-5,6-diphenyl-1,2,4-triazine and dppm: Bis(diphenylphosphino)methane], was prepared and characterized by IR, 1H-NMR, 31P-NMR spectroscopy, elemental and thermogravimetric analysis, and a single-crystal X-ray diffraction technique. Complex 1 is a dinuclear compound, showing that L and dppm act as tridentate and bidentate chelating ligands, respectively. The two Cu(I) atoms exhibit a distorted tetrahedral coordination sphere embedded in N3P environments. The supramolecular interactions in the solid-state structure are characterized by C−H···N, C−H···F, C-H···π and π···π intermolecular interactions, which we studied using Hirshfeld surface and fingerprint tools. Additionally, the complex was studied experimentally using UV–Vis spectroscopy and cyclic voltammetry, and theoretical studies with time-dependent density functional theory (TD-DFT) were performed. Moreover, the optical and electrochemical properties were studied, focusing on the band gap. Compound 1 was used as a co-sensitizer in a dye-sensitized solar cell, showing a good photovoltaic performance of 2.03% (Jsc = 5.095 mAcm−2, Voc = 757 mV, and FF = 52.7%) under 100 mW cm−2 (AM 1.5G) solar irradiation, which is similar to that of DSSC, which was only sensitized by N719 (2.2%) under the same condition.

Molecules sourced from marine environments hold immense promise for the development of novel therapeutic drugs, owing to their distinctive chemical compositions and valuable medicinal attributes. Notably, Talarolide A and Talaropeptides A–D have gained recent attention as potential candidates for pharmaceutical applications. This study aims to explore the chemical reactivity of Talarolide A and Talaropeptides A–D through the application of molecular modeling and computational chemistry techniques, specifically employing Conceptual Density Functional Theory (CDFT). By investigating their chemical behaviors, the study seeks to contribute to the understanding of the potential pharmacological uses of these marine-derived compounds. The molecular geometry optimizations and frequency calculations were conducted using the Density Functional Tight Binding (DFTBA) method. This was followed by a subsequent round of geometry optimization, frequency analysis, and computation of electronic properties and chemical reactivity descriptors. We employed the MN12SX/Def2TZVP/H2O model chemistry, utilizing the Gaussian 16 program and the SMD solvation model. The analysis of the global reactivity descriptors arising from CDFT was achieved as well as the graphical comparison of the dual descriptor DD revealing the areas of the molecules with more propensity to suffer a nucleophilic or electrophilic attack. Additionally, Molinspiration and SwissTargetPrediction were considered for the calculation of molecular characteristics and predicted biological targets. These include enzymes, nuclear receptors, kinase inhibitors, GPCR ligands, and ion channel modulators. The graphical results show that Talarolide A and the Talaropeptides A–D are likely to behave as protease inhibitors.

Este número de Mundo Nano reúne investigaciones computacionales de modelado de nanomateriales y estudios de interés en NyN, que impulsan la innovación y el avance científico en áreas como medicina, electrónica, remediación ambiental y energía, proveyendo una panorámica de las investigaciones que se realizan actualmente en México en este campo de estudio.

This paper reports the results of a computational nanochemistry study of the chemical reactivities and bioactivity properties of two antimicrobial peptides using a CDFT-based computational peptidology (CDFT-CP) methodology, which is derived from the combination of the chemical reactivity descriptors derived from conceptual density functional theory (CDFT) and some cheminformatics tools useful in the design of therapeutic drugs. This is complemented by an examination of the bioactivity and pharmacokinetics indices of the peptides in relation to the ADMET (absorption, distribution, metabolism, excretion, and toxicity) features. These findings provide further evidence of the superiority of the MN12SX density functional in fulfilling the Janak and ionization energy theorems using an earlier proposed KID methodology for validation. This has proven to be beneficial in accurately predicting CDFT indices, which is of help in the understanding of the chemical reactivity. The computational pharmacokinetics study revealed the potential ability of both cyclopeptides as therapeutic drugs through the interaction with different target receptors. The ADMET indices confirmed this assertion through the absence of toxicity and good absorption and distribution properties.

Breast cancer is the second most common malignancy in females worldwide and poses a great challenge that necessitates the identification of novel therapeutic agents from several sources. This research aimed to study the molecular docking and molecular dynamics simulations of four proteins (such as PDB: 6CBZ, 1FDW, 5GWK and 2WTT) with the selected phytochemicals from Withania somnifera to identify the potential inhibitors for breast cancer. The molecular docking result showed that among 44 compounds, two of them, Ashwagandhanolide and Withanolide sulfoxide have the potential to inhibit estrogen receptor alpha (ERα), 17-beta-hydroxysteroid -dehydrogenase type 1 (17β-HSD1), topoisomerase II alpha (TOP2A) and p73 tetramerization domain that are expressed during breast cancer. The molecular dynamics (MD) simulations results suggested that Ashwagandhanolide remained inside the binding cavity of four targeted proteins and contributed favorably towards forming a stable protein-ligand complex throughout the simulation. Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties confirmed that Ashwagandhanolide is hydrophobic and has moderate intestinal permeability, good intestinal absorption, and poor skin permeability. The compound has a relatively low VDss value (-1.652) and can be transported across ABC transporter and good central nervous system (CNS) permeability but did not easily cross the blood-brain barrier (BBB). This compound does not possess any mutagenicity, hepatotoxicity and skin sensitization. Based on the results obtained, the present study highlights the anticancer potential of Ashwagandhanolide, a compound from W. somnifera. Furthermore, in vitro and in vivo studies are necessary to perform before clinical trials to prove the potentiality of Ashwagandhanolide.

Over the years, Alzheimer’s disease (AD) treatments have been a major focus, culminating in the identification of promising therapeutic targets. A herbal therapy approach has been required by the demand of AD stage-dependent optimal settings. Present study describes the evaluation of anti-acetylcholinesterase (AChE) activity of hydroxyapatite nanoparticles derived from an Acorus calamus rhizome extract (AC-HAp NPs). The structure and morphology of as-prepared (AC-HAp NPs) was confirmed using powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HR-TEM). The crystalline nature of as-prepared AC-HAp NPs was evident from XRD pattern. The SEM analysis suggested the spherical nature of the synthesized material with an average diameter between 30 and 50 nm. Further, the TEM and HR-TEM images revealed the shape and size of as-prepared (AC-HAp NPs). The interplanar distance between two lattice fringes was found to be 0.342 nm, which further supported the crystalline nature of the material synthesized. The anti-acetylcholinesterase activity of AC-HAp NPs was greater as compared to that of pure HAp NPs. The mechanistic evaluation of such an activity carried out using in silico studies suggested that the anti-acetylcholinesterase activity of phytoconstituents derived from Acorus calamus rhizome extract was mediated by BNDF, APOE4, PKC-γ, BACE1 and γ-secretase proteins. The global and local descriptors, which are the underpinnings of Conceptual Density Functional Theory (CDFT), have been predicted through the MN12SX/Def2TZVP/H2O model chemistry to help in the comprehension of the chemical reactivity properties of the five ligands considered in this study. With the further objective of analyzing their bioactivity, the CDFT studies are complemented with the estimation of some useful computed pharmacokinetics indices, their predicted biological targets, and the ADMET parameters related to the bioavailability of the five ligands are also reported.

The ever-expanding pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has gained attention as COVID-19 and caused an emergency in public health to an unmatched level to date. However, the treatments used are the only options; currently, no effective and licensed medications are available to combat disease transmission, necessitating further research. In the present study, an in silico-based virtual screening of anti-HIV bioactive compounds from medicinal plants was carried out through molecular docking against the main protease (Mpro) (PDB: 6LU7) of SARS-CoV-2, which is a key enzyme responsible for virus replication. A total of 16 anti-HIV compounds were found to have a binding affinity greater than −8.9 kcal/mol out of 150 compounds screened. Pseudohypericin had a high affinity with the energy of −10.2 kcal/mol, demonstrating amino acid residual interactions with LEU141, GLU166, ARG188, and GLN192, followed by Hypericin (−10.1 kcal/mol). Moreover, the ADME (Absorption, Distribution, Metabolism and Excretion) analysis of Pseudohypericin and Hypericin recorded a low bioavailability (BA) score of 0.17 and violated Lipinski’s rule of drug-likeness. The docking and molecular simulations indicated that the quinone compound, Pseudohypericin, could be tested in vitro and in vivo as potent molecules against COVID-19 disease prior to clinical trials.This was also supported by the theoretical and computational studies conducted. The global and local descriptors, which are the underpinnings of Conceptual Density FunctionalTheory (CDFT) have beenpredicted through successful model chemistry, hoping that they could be of help in the comprehension of the chemical reactivity properties of the molecular systems considered in this study.

Herein we describe the synthesis of a series of nickel(II) complexes (C1–C3) with Schiff bases (HL1–HL3) derived from 4-amino-5-mercapto-3-methyl-1,2,4-triazole and ortho/meta/para-nitrobenzaldehyde having composition [Ni(L)2(H2O)2]. The obtained ligands and their complexes were characterized using physico-chemical techniques viz., elemental analysis, magnetic moment study, spectral (electronic, FT-IR, 1H-NMR) and thermal analysis. The elemental analysis and spectral analysis revealed that Schiff bases behave as monoanionic bidentate ligands towards the Ni(II) ion. Whereas, the magnetic moment study suggested the octahedral geometry of all the Ni(II) complexes. The thermal behavior of the complexes has been studied by thermogravimetric analysis and agrees well with the composition of complexes. Further, the biological activities such as antimicrobial and antifungal studies of the Schiff bases and Ni(II) complexes have been screened against bacterial species (Staphylococcus aureus and Pseudomonas aeruginosa) and fungal species (Aspergillus niger and Candida albicans) activity by MIC method, the results of which revealed that metal complexes exhibited significant antimicrobial activities than their respective ligands against the tested microbial species. Furthermore, the molecular docking technique was employed to investigate the active sites of the selected protein, which indeed helped us to screen the potential anticancer agents among the synthesized ligand and complexes. Further, these compounds have been screened for their in vitro anticancer activity using OVCAR-3 cell line. The results revealed that the complexes are more active than the ligands.

This research presents the outcomes of a computational determination of the chemical reactivity and bioactivity properties of two plant cyclopeptides isolated from Rosaceae through the consideration of Computational Peptidology (CP), a protocol employed previously in the research of similar molecular systems. CP allows the prediction of the global and local descriptors that are the integral foundations of Conceptual Density Functional Theory (CDFT) and which could help in getting in the understanding of the chemical reactivity properties of the two plant cyclopeptides under study, hoping that they could be related to their bioactivity. The methodology based on the Koopmans in DFT (KID) approach and the MN12SX/Def2TZVP/H2O model chemistry has been successfully validated. Various Chemoinformatics tools have been used to improve the process of virtual screening, thus identifying some additional properties of these two plant cyclopeptides connected to their ability to behave as potentially useful drugs. With the further objective of analyzing their bioactivity, the CP protocol is complemented with the estimation of some useful parameters related to pharmacokinetics, their predicted biological targets, and the Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) parameters related to the bioavailability of the two plant cyclopeptides under study are also reported.

Abstract Objective A well-behaved model chemistry previously validated for the study of the chemical reactivity of peptides was considered for the calculation of the molecular properties and structure of the Taltobulin anticancer peptide. A methodology based on Conceptual Density Functional Theory (CDFT) was chosen for the determination of the reactivity descriptors. Results The molecular active sites were associated with the active regions of the molecule were associated with the nucleophilic and electrophilic Fukui functions. Finally, the bioactivity scores for the Taltobulin peptide are predicted through a homology methodology relating them with the calculated reactivity descriptors.

New copper(I) compounds of compositions [Cu(HL)(PPh3)2]·H2O (1) and [Cu(HL)POP]·CH2Cl2 (2), where HL = monoanion of pyridine-2,5-dicarboxylic acid, PPh3 = triphenylphosphine and POP = bis [2-(diphenylphosphine)phenyl]ether), are documented. The complexes were characterized by elemental analysis, spectroscopic techniques (IR, 1H/31P RMN and UV–VIS), cyclic voltammetry, and thermogravimetric analysis. Single-crystals for 1 and 2 enabled X-ray diffraction analysis, revealing distorted tetrahedral geometries for Cu(I) centers embedded in NOP2 environments. The crystal structures are stabilized by O−H∙∙∙O, C−H∙∙∙O, C−H∙∙∙π and π∙∙∙π interactions that were analyzed by inspection of the Hirshfeld surfaces and fingerprint plots. Compounds 1 and 2 show interesting optical/electrochemical properties, which were studied experimentally in solution by UV–Vis spectroscopy and cyclic voltammetry, as well as theoretically using Time-Dependent Density Functional Theory (TD-DFT). Additionally, in combination with the ruthenium complex N719, their efficiency as co-sensitizers in dye-sensitized solar cells (DSSCs) was assessed, showing good activity.

Annona muricata, a tropical plant which has been extensively used in ethnomedicine to treat a wide range of diseases, from malaria to cancer. Interestingly, this plant has been reported to demonstrate significant antiviral properties against the human immunodeficiency virus, herpes simplex virus, human papilloma virus, hepatitis C virus and dengue virus. Additionally, the bioactive compounds responsible for antiviral efficacy have also shown to be selectively cytotoxic while inhibiting tumorigenic cell growth without affecting the normal cell growth. Annonaceous Acetogenins are a class of bioactive compounds exclusive to the Annonaceae family at which the plant A. muricata belongs. In the current study, we have created a library of Acetogenins unique to the plant, comprising of Annomuricin A, Annomuricin B, Annomuricin C, Muricatocin C, Muricatacin, cis-Annonacin, Annonacin-10-one, cis-Goniothalamicin, Arianacin and Javoricin, for in silico and theoretical evaluations against the SARS-CoV-2 spike protein in an attempt toward promotion of plant based drug development for the current pandemic of coronavirus disease 2019 (COVID-19). We found that all the Acetogenins showing in silico spike protein significantly docking with good binding affinities. Moreover, we envision A. muricata Acetogenins can be further studied by in vitro and in vivo models to identify potential anti-SARS-CoV-2 agents.

Alternaramide is a cyclic pentadepsipeptide isolated from marine sources that has been shown to present weak antibiotic activity against Bacillus subtilis and Staphylococcus aureus as well as inhibitory effects on inflammatory mediator expressions. Thus, this work reports the results of a computational study of the chemical reactivity and bioactivity properties of this cyclopentadepsipeptide considering a CDFT-based computational peptidology (CDFT-CP) methodology that results from the combination of the chemical reactivity descriptors that arise from conceptual density functional theory (CDFT) together with some cheminformatics tools that can be used to estimate the associated physicochemical parameters, to improve the process of virtual screening through a similarity search, and to identify the ability of the peptide to behave as a potential useful drug, complemented with an analysis of its bioactivity and pharmacokinetics indices related to the ADMET (absorption, distribution, metabolism, excretion, and toxicity) features. The results represent a new confirmation of the superiority of the MN12SX density functional in the fulfilment of the Janak and ionization energy theorems through the proposed KID procedure. This has been useful for the accurate prediction of the CDFT reactivity descriptors that help in understanding the chemical reactivity. The computational pharmacokinetics study revealed the potential ability of alternaramide as a therapeutic drug by interacting with GPCR ligands and protease inhibitors. The ADMET indices confirm this assertion through the absence of toxicity and good absorption and distribution properties.

8-Hydroxyquinolin-5-sulfonic acid (8HQSA) was combined with 3-pyridineboronic acid (3PBA) or 4-pyridineboronic acid (4PBA) to give two zwitterionic monoboron complexes in crystalline form. The compounds were characterized by elemental analysis, single-crystal X-ray diffraction studies, and IR, 1H NMR, UV-Visible, and luminescence spectroscopy. The analyses revealed compounds with boron atoms adopting tetrahedral geometry. In the solid state, the molecular components are linked by charge-assisted (B)(O−H⋯−O(S) and N+−H⋯O(S) hydrogen bonds aside from C−H⋯O contacts and π⋯π interactions, as shown by Hirshfeld surface analyses and 2D fingerprint plots. The luminescence properties were characterized in terms of the emission behavior in solution and the solid state, showing emission in the bluish-green region in solution and large positive solvatofluorochromism, caused by intramolecular charge transfer. According to TD-DFT calculations at the M06-2X/6-31G(d) level of theory simulating an ethanol solvent environment, the emission properties are originated from π-π * and n-π * HOMO-LUMO transitions.

Bioactive peptides are chemical compounds created through the covalent bonding of amino acids, known as amide or peptide bonds. Due to their unusual chemistry and various biological effects, marine bioactive peptides have garnered considerable research. The effectiveness of a bioactive marine peptide is attributed to its structural features, such as amino acid content and sequence, which vary depending on the degree of action. Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity and low toxicity that render them an attractive modality for the development of therapeutics. The apratoxins are a class of molecules formed by a series of cyclic depsipeptides with potent cytotoxic activities. The objective of this research is to pursue a computational prospection of the molecular structures and properties of several cylopeptides of marine origin with potential therapeutic applications. The methodology will be based on the determination of the chemical reactivity descriptors of the studied molecules through the consideration of the Conceptual DFT model and validation of a particular model chemistry, MN12SX/Def2TZVP/H2O. These studies will be complemented by a determination of the pharmacokinetics and ADMET parameters by resorting to certain cheminformatics tools.

Researchers are interested in Schiff bases and their metal complexes because they offer a wide range of applications. The chemistry of Schiff bases of heterocompounds has got a lot of attention because of the metal’s ability to coordinate with Schiff base ligands. In the current study, a new bidentate Schiff base ligand, N-((1H-pyrrol-2-yl)methylene)-6-methoxypyridin-3-amine (MPM) has been synthesized by condensing 6-methoxypyridine-3-amine with pyrrole-2-carbaldehyde. Further, MPM is used to prepare Cu(II) and Co(II) metal complexes. Analytical and spectroscopic techniques are used for the structural elucidation of the synthesized compounds. Both MPM and its metal complexes were screened against Escherichia coli, Bacillus subtilis, Staphylococcus aureus and Klebsiella pneumoniae species for antimicrobial studies. Furthermore, these compounds were subjected to in silico studies against bacterial proteins to comprehend their best non-bonded interactions. The results confirmed that the Schiff base ligand show considerably higher binding affinity with good hydrogen bonding and hydrophobic interactions against various tested microbial species. These results were complemented with a report of the Conceptual DFT global reactivity descriptors of the studied compounds together with their biological scores and their ADMET computed parameters.

As a continuation of our research on the chemical reactivity, pharmacokinetics and ADMET properties of cyclopeptides of marine origin with potential therapeutic abilities, in this work our already presented integrated molecular modeling protocol has been used for the study of the chemical reactivity and bioactivity properties of the Veraguamides A–G family of marine natural drugs. This protocol results from the estimation of the conceptual density functional theory (CDFT) chemical reactivity descriptors together with several chemoinformatics tools commonly considered within the process of development of new therapeutic drugs. CP-CDFT is a branch of computational chemistry and molecular modeling dedicated to the study of peptides, and it is a protocol that allows the estimation with great accuracy of the CDFT-based reactivity descriptors and the associated physical and chemical properties, which can aid in determining the ability of the studied peptides to behave as potential useful drugs. Moreover, the superiority of the MN12SX density functional over other long-range corrected density functionals for the prediction of chemical and physical properties in the presence of water as the solvent is clearly demonstrated. The research was supplemented with an investigation of the bioactivity of the molecular systems and their ADMET (absorption, distribution, metabolism, excretion, and toxicity) parameters, as is customary in medicinal chemistry. Some instances of the CDFT-based chemical reactivity descriptors’ capacity to predict the pKas of peptides as well as their potential as AGE inhibitors are also shown.

NAD(P)H:quinone acceptor oxidoreductase-1 (NQO1) is a ubiquitous flavin adenine dinucleotide-dependent flavoprotein that promotes obligatory two-electron reductions of quinones, quinonimines, nitroaromatics, and azo dyes. NQO1 is a multifunctional antioxidant enzyme whose expression and deletion are linked to reduced and increased oxidative stress susceptibilities. NQO1 acts as both a tumor suppressor and tumor promoter; thus, the inhibition of NQO1 results in less tumor burden. In addition, the high expression of NQO1 is associated with a shorter survival time of cancer patients. Inhibiting NQO1 also enables certain anticancer agents to evade the detoxification process. In this study, a series of phytobioactives were screened based on their chemical classes such as coumarins, flavonoids, and triterpenoids for their action on NQO1. The in silico evaluations were conducted using PyRx virtual screening tools, where the flavone compound, Orientin showed a better binding affinity score of −8.18 when compared with standard inhibitor Dicumarol with favorable ADME properties. An MD simulation study found that the Orientin binding to NQO1 away from the substrate-binding site induces a potential conformational change in the substrate-binding site, thereby inhibiting substrate accessibility towards the FAD-binding domain. Furthermore, with this computational approach we are offering a scope for validation of the new therapeutic components for their in vitro and in vivo efficacy against NQO1.

A methodology based on the concepts that arise from Density Functional Theory (CDFT) was chosen for the calculation of the global and local reactivity descriptors of the Phallotoxin family of fungal peptides. The determination of the active sites for the molecules has been achieved by resorting some descriptors within Molecular Electron Density Theory (MEDT) like the Dual Descriptor and the Parr functions. Phallosacin has been found as the most reactive of the peptides on the basis of the calculated Global Reactivity Descriptors. The pKas of the seven studied peptides were established using a proposed relationship between this property and the calculated Global Hardness. The bioactivity properties of the peptides considered in this study were obtained by resorting to a homology model by comparison with the bioactivity of related molecules in their interaction with different receptors.

Five density functionals, CAM-B3LYP, LC-ωHPBE, MN12SX, N12SX, and ωB97XD, in connection with the Def2TZVP basis set were assessed together with the SMD solvation model for the calculation of the molecular properties, chemical reactivities, and solubilities of some pigments derived from astaxanthin, β-cryptoxanthin, fucoxanthin, myxol, siphonaxanthin, siphonein, and zeaxanthin marine carotenoids in the presence of different solvents (hexane, methanol, ethanol, and water). All the chemical reactivity descriptors for the systems were calculated via conceptual density functional theory (CDFT). Finally, the potential bioavailability and druggability as well as the bioactivity scores for the marine carotenoid pigments were predicted through different methodologies already reported in the literature, which have been previously validated during the study of other natural products obtained from marine sources.

Candida albicans, an opportunistic fungal pathogen, frequently colonizes immune-compromised patients and causes mild to severe systemic reactions. Only few antifungal drugs are currently in use for therapeutic treatment. However, evolution of a drug-resistant C. albicans fungal pathogen is of major concern in the treatment of patients, hence the clinical need for novel drug design and development. In this study, in vitro screening of novel putative pyrrolo[1,2-a]quinoline derivatives as the lead drug targets and in silico prediction of the binding potential of these lead molecules against C. albicans pathogenic proteins, such as secreted aspartic protease 3 (SAP3; 2H6T), surface protein β-glucanase (3N9K) and sterol 14-alpha demethylase (5TZ1), were carried out by molecular docking analyses. Further, biological activity-based QSAR and theoretical pharmacokinetic analysis were analyzed. Here, in vitro screening of novel analogue derivatives as drug targets against C. albicans showed inhibitory potential in the concentration of 0.4 µg for BQ-06, 07 and 08, 0.8 µg for BQ-01, 03, and 05, 1.6 µg for BQ-04 and 12.5 µg for BQ-02 in comparison to the standard antifungal drug fluconazole in the concentration of 30 µg. Further, in silico analysis of BQ-01, 03, 05 and 07 analogues docked on chimeric 2H6T, 3N9K and 5TZ1 revealed that these analogues show potential binding affinity, which is different from the therapeutic antifungal drug fluconazole. In addition, these molecules possess good drug-like properties based on the determination of conceptual Density Functional Theory (DFT)-based descriptors, QSAR and pharmacokinetics. Thus, the study offers significant insight into employing pyrrolo[1,2-a]quinoline analogues as novel antifungal agents against C. albicans that warrants further investigation.

Herein, we report the synthesis and characterization of a new Schiff base ligand 3-[[(E)-(3-hydroxyphenyl)-methylidene]amino]-2-methyl-quinazolin-4(3H)-one (HAMQ) and its Cd(II), Ni(II), Zn(II), and Cu(II) complexes (C1–C4). The ligand HAMQ was synthesized by reacting 3-hydroxybenzaldehyde and 3-amino-2-methyl-4(3H)-quinazolinone in a 1:1 molar ratio. The structure of the ligand and its complexes (C1–C4) were evaluated using ultraviolet (UV)–visible (Vis) light spectroscopy, 1H-NMR, Fourier-transform infrared (FT-IR) spectroscopy, MS, elemental analysis, conductance data, and thermogravimetric analysis (TGA). The characterization results suggested that the bidentate ligand, HAMQ, coordinated to the metal center through the lactum oxygen and the azomethine nitrogen. Moreover, all the metal complexes were analyzed using powder X-ray diffraction studies, which revealed that all of them belong to a triclinic crystal system. The research was supplemented by density functional theory (DFT) studies on the IR and UV–Vis spectra, as well as the chemical reactivity of the HAMQ and its four metallic derivatives making use of conceptual density functional theory (CDFT) by means of KID (Koopmans in DFT) methodology. The synthesized complexes displayed significant in vitro anticancer activity against human cancer cell lines (HeLa and HCT-115).

A methodology based on the concepts that arise from Density Functional Theory named Conceptual Density Functional Theory (CDFT) was chosen for the calculation of some global and local reactivity descriptors of the Discodermins A–H family of marine peptides through the consideration of the KID (Koopmans in DFT) technique that was successfully used in previous studies of this kind of molecular systems. The determination of active sites of the studied molecules for different kinds of reactivities was achieved by resorting to some CDFT-based descriptors like the Fukui functions as well as the Parr functions derived from Molecular Electron Density Theory (MEDT). A few properties identified with their ability to behave as a drug and the bioactivity of the peptides considered in this examination were acquired by depending on a homology model by studying the correlation with the known bioactivity of related molecules in their interaction with various biological receptors. With the further object of analyzing their bioactivity, some parameters of usefulness for future QSAR studies, their predicted biological targets, and the ADME (Absorption, Distribution, Metabolism, and Excretion) parameters related to the Discodermins A–H pharmacokinetics are also reported.

This work presents the results of a computational study of the chemical reactivity and bioactivity properties of the members of the theopapuamides A-D family of marine peptides by making use of our proposed methodology named Computational Peptidology (CP) that has been successfully considered in previous studies of this kind of molecular system. CP allows for the determination of the global and local descriptors that come from Conceptual Density Functional Theory (CDFT) that can give an idea about the chemical reactivity properties of the marine natural products under study, which are expected to be related to their bioactivity. At the same time, the validity of the procedure based on the adoption of the KID (Koopmans In DFT) technique, as well as the MN12SX/Def2TZVP/H2O model chemistry is successfully verified. Together with several chemoinformatic tools that can be used to improve the process of virtual screening, some additional properties of these marine peptides are identified related to their ability to behave as useful drugs. With the further objective of analyzing their bioactivity, some useful parameters for future QSAR studies, their predicted biological targets, and the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) parameters related to the theopapuamides A-D pharmacokinetics are also reported.

Eight novel metal-free organic sensitizers were proposed for dye-sensitized solar cells (DSSCs), theoretically calculated and studied via density functional theory with D-π-A structure. These proposals were formed to study the effect of novel π-bridges, using carbazole as the donor group and cyanoacrylic acid as the anchorage group. Through the M06/6-31G(d) level of theory, ground state geometry optimization, vibrational frequencies, the highest occupied molecular orbital, the lowest unoccupied molecular orbital, and their energy levels were calculated. Further, chemical reactivity parameters were obtained and analyzed, such as chemical hardness (η), electrophilicity index (ω), electroaccepting power (ω+) and electrodonating power (ω-). Free energy of electron injection (ΔGinj) and light-harvesting efficiency (LHE) also were calculated and discussed. On the other hand, absorption wavelengths, oscillator strengths, and electron transitions were calculated through time-dependent density functional theory with the M06-2X/6-31G(d) level of theory. In conclusion, the inclusion of thiophene groups and the Si heteroatom in the π-bridge improved charge transfer, chemical stability, and other optoelectronic properties of carbazole-based dyes.

In this paper, the antiestrogenic properties of Tamoxifen analogs have been investigated and a theoretical report of its analogs interaction with the pocket site of some hormone receptors are presented. Analogs were generated by modification of the hydrophilic functional group of Tamoxifen by hydroxyl, amide, carboxyl, and sulfhydryl functional groups, in an attempt to improve their activity and selectivity. The analogs exhibit a negative binding energy in the estrogen and progesterone receptors, which indicates a spontaneous interaction between the analogs and the pocket site in the hormone receptors. The values of the molecular polar surface area indicate that the analogs have good permeability and are strong electrophiles. The couplings showed electrostatic interactions such as hydrogen bond and π-π interactions. According with the Lipinsky Rule of Five, the four analogs presented a good biodistribution, permeability, and pharmacological action on the hormone receptors. The analysis of the charge transfer suggests a limited enhanced oxidative damage in the estrogen receptor that not takes place with the progesterone receptor.

This computational study assessed eight fixed RSH (range-separated hybrid) density functionals that include CAM-B3LYP, LC-ωPBE, M11, MN12SX, N12SX, ωB97, ωB97X, and ωB97XD related to the Def2TZVP basis sets together with the SMD solvation model in the calculation the molecular structure and reactivity properties of the BISARG intermediate melanoidin pigment (5-(2-(E)-(Z)-5-[(2-furyl)methylidene]-3-(4-acetylamino-4-carboxybutyl)-2-imino-1,3-dihydroimidazol-4-ylideneamino(E)-4-[(2-furyl)methylidene]-5-oxo-1H-imidazol-1-yl)-2-acetylaminovaleric acid) and its protonated derivative, BISARG(p). The chemical reactivity descriptors for the systems were calculated via the Conceptual Density Functional Theory. The choice of active sites applicable to nucleophilic, electrophilic as well as radical attacks were made by linking them with Fukui functions indices, electrophilic and nucleophilic Parr functions, and the condensed Dual Descriptor Δf(r). The study found the MN12SX and N12SX density functionals to be the most appropriate in predicting the chemical reactivity of the molecular systems under study starting from the knowledge of the HOMO, LUMO, and HOMO-LUMO gap energies.

This study evaluated a fixed long-range corrected range-separated hybrid (RSH) density functional associated with the Def2TZVP basis set alongside the SMD solvation model for the computation of the structure, molecular properties, and chemical reactivity of the M8 intermediate melanoidin pigment in the presence of water and dioxane. The preference of the active sites pertinent to radical, nucleophilic, and electrophilic attacks is made through linking them with the electrophilic and nucleophilic Parr functions, Fukui function indices, and condensed dual descriptor which are chemical reactivity descriptors that arise from conceptual density functional theory. The study confirmed the results from previous works showing that the MN12SX density functional is the most appropriate in predicting the chemical reactivity of this molecule in both solvents.

Ten molecules were theoretically calculated and studied through density functional theory with the M06 density functional and the 6-31G(d) basis set. The molecular systems have potential applications as sensitizers for dye-sensitized solar cells. Three molecules were taken from the literature, and seven are proposals inspired in the above, including the azomethine group in the π-bridge expecting a better charge transfer. These molecular structures are composed of triphenylamine (donor part); different combinations of azomethine, thiophene, and benzene derivatives (π-bridge); and cyanoacrylic acid (acceptor part). This study focused on the effect that the azomethine group caused on the π-bridge. Ground-state geometry optimization, the highest occupied molecular orbital, the lowest unoccupied molecular orbital, and their energy levels were obtained and analyzed. Absorption wavelengths, oscillator strengths, and electron transitions were obtained via time-dependent density functional theory using the M06-2X density functional and the 6-31G(d) basis set. The free energy of electron injection (ΔGinj) was calculated and analyzed. As an important part of this study, chemical reactivity parameters are discussed, such as chemical hardness, electrodonating power, electroaccepting power, and electrophilicity index. In conclusion, the inclusion of azomethine in the π-bridge improved the charge transfer and the electronic properties of triphenylamine-based dyes.

A well-behaved model chemistry previously validated for the study of the chemical reactivity of peptides was considered for the calculation of the molecular properties and structures of the Papuamide family of marine peptides. A methodology based on Conceptual Density Functional Theory (CDFT) was chosen for the determination of the reactivity descriptors. The molecular active sites were associated with the active regions of the molecules related to the nucleophilic and electrophilic Parr functions. Finally, the drug-likenesses and the bioactivity scores for the Papuamide peptides were predicted through a homology methodology relating them with the calculated reactivity descriptors, while other properties such as the pKas were determined following a methodology developed by our group.

A methodology based on concepts that arose from Density Functional Theory (CDFT) was chosen for the calculation of global and local reactivity descriptors of the Seragamide family of marine anticancer peptides. Determination of active sites for the molecules was achieved by resorting to some descriptors within Molecular Electron Density Theory (MEDT) such as Fukui functions. The pKas of the six studied peptides were established using a proposed relationship between this property and calculated chemical hardness. The drug likenesses and bioactivity properties of the peptides considered in this study were obtained by resorting to a homology model by comparison with the bioactivity of related molecules in their interaction with different receptors. With the object of analyzing the concept of drug repurposing, a study of potential AGE-inhibition abilities of Seragamides peptides was pursued by comparison with well-known drugs that are already available as pharmaceuticals.

Virotoxins are monocyclic peptides formed by at least five different compounds: alaviroidin, viroisin, deoxoviroisin, viroidin and deoxovirodin. These are toxic peptides singularly found in Amanita virosa mushrooms. Here we perform computational studies on the structural and electronic conformations of these peptides using the MN12SX/Def2TZVP/H2O chemistry model to investigate their chemical reactivity. CDFT-based descriptors (for Conceptual Density Functional Theory) (e.g., Parr functions and Nucleophilicity) are also considered. At the same time, other properties (e.g., pKas) will be determined and used to study virotoxins solubility and to inform decisions about repurposing these agents in medicinal chemistry.

This work presents an account of the reactivity behavior of the anticancer marine drugs, Soblidotin and Tasidotin, based on the calculation of the global and local descriptors resulting from Chemical Reactivity Theory (CRT), also known as Conceptual DFT, for their consideration as a useful complement to approximations based on Molecular Docking. The information on the global and local reactivity descriptors of the Soblidotin and Tasidotin molecules, obtained through our proposed methodology, may be used for the design of new pharmaceutical analogs by relying on the chemical interactions between these peptides and their protein-type biological receptors. It can be concluded that the CRT approximation to the global and local chemical reactivity, based on the descriptors, can provide interesting information for the consideration of both molecules as potential therapeutic drugs. This is complemented by a study on Advanced Glycation Endproduct (AGE) inhibition, by comparison with the usual molecular systems considered for the task, as a re-purposing study. Finally, the bioactivity scores for Soblidotin and Tasidotin are predicted through an empirical procedure, based on comparison with molecular structures with well-known pharmacological properties.

Eight coumarin derivative dyes were studied by varying the π-bridge size with different thiophene and thiazole units for their potential use in dye-sensitized solar cells (DSSC). Geometry optimization, the energy levels and electron density of the Highest Occupied Molecular Orbital and the Lowest Unoccupied Molecular Orbital, and ultraviolet-visible absorption spectra were calculated by Density Functional Theory (DFT) and Time-Dependent-DFT. All molecular properties were analyzed to decide which dye was the most efficient. Furthermore, chemical reactivity parameters, such as chemical hardness, electrophilicity index, and electroaccepting power, were obtained and analyzed, whose values predicted the properties of the dyes in addition to the rest of the studied molecular properties. Our calculations allow us to qualitatively study dye molecules and choose the best for use in a DSSC. The effects of π-bridges based on thiophenes, thiazoles, and combinations of the two were reviewed; dyes with three units mainly of thiazole were chosen as the best photosensitizers for DSSC.

The MN12SX density functional, in connection with the Def2TZVP basis set, was assessed, together with the SMD solvation model (Solvation Model based on the Density), for calculation of the molecular properties and structure of a group of peptides of marine origin named Mirabamides A–H. All the chemical reactivity descriptors for the systems were calculated via Conceptual Density Functional Theory (CDFT). The active sites suitable for nucleophilic, electrophilic, and radical attacks were chosen by linking them with the Fukui function indices, nucleophilic and electrophilic Parr functions, and condensed Dual Descriptor Δ f ( r ) , respectively. Additionally, the p K a values for the different peptides are predicted with great accuracy as well as the ability of the studied molecule in acting as an efficient inhibitor of the formation of Advanced Glycation Endproducts (AGEs), which constitutes a useful knowledge for the development of drugs for fighting Diabetes, Alzheimer and Parkinson diseases. Finally, the bioactivity scores for the Mirabamides A–H are predicted through different methodologies.

In this work several natural carotenoids were studied as potential nanomaterial precursors for molecular photovoltaics. M05-2X/6-31+G(d,p) level of theory calculations were used to obtain their molecular structures, as well as to predict the infrared (IR) and ultraviolet (UV-Vis) spectra, the dipole moment and polarizability, the pKa, and the chemical reactivity parameters (electronegativity, hardness, electrophilicity and Fukui functions) that arise from Conceptual DFT. The calculated values were compared with the available experimental data for these molecules and discussed in terms of their usefulness in describing photovoltaic properties.

This computational study presents the assessment of eleven density functionals that include CAM-B3LYP, LC-wPBE, M11, M11L, MN12L, MN12SX, N12, N12SX, wB97, wB97X and wB97XD related to the Def2TZVP basis sets together with the Solvation Model Density (SMD) solvation model in calculating the molecular properties and structure of the Blue-G1 intermediate melanoidin pigment. The chemical reactivity descriptors for the system are calculated via the conceptual Density Functional Theory (DFT). The choice of the active sites related to the nucleophilic, electrophilic, as well as radical attacks is made by linking them with the Fukui function indices, the electrophilic Parr functions and the condensed dual descriptor Δ f ( r ) . The prediction of the maximum absorption wavelength tends to be considerably accurate relative to its experimental value. The study found the MN12SX and N12SX density functionals to be the most appropriate density functionals in predicting the chemical reactivity of the studied molecule.

Polythiophene (PTh) and its derivatives are polymer-based materials with a π-conjugation framework. PTh is a useful photoelectric material and can be used in organic semiconductor devices, such as PLED, OLED, and solar cells. Their properties are based on molecular structure; the derivatives contain different substitutes in the 3 and 5 positions, such as electron-donating or electron-withdrawing groups. All molecular geometries were optimized at B3LYP/6-31G(d,p) level of theory. The energy gap (Egap) between the HOMO and LUMO levels is related to the π-conjugation in the PTh polymer backbone. In this study, the DFT calculations were performed for the nonsubstituted and 3,5-substituted variants to investigate the stability geometries and electrical properties. The theoretical calculations show that the substituted forms are stable, have low Egap, and are in good agreement with the experimental observations.

The use of nanodiamonds as anticancer drug delivery vehicles has received much attention in recent years. In this theoretical paper, we propose using different esterification methods for nanodiamonds. The monomers proposed are 2-hydroxypropanal, polyethylene glycol, and polyglicolic acid. Specifically, the hydrogen bonds, infrared (IR) spectra, molecular polar surface area, and reactivity parameters are analyzed. The monomers proposed for use in esterification follow Lipinski’s rule of five, meaning permeability is good, they have good permeation, and their bioactivity is high. The results show that the complex formed between tamoxifen and nanodiamond esterified with polyglicolic acid presents the greatest number of hydrogen bonds and a good amount of molecular polar surface area. Calculations concerning the esterified nanodiamond and reactivity parameters were performed using Density Functional Theory with the M06 functional and the basis set 6–31G (d); for the esterified nanodiamond–Tamoxifen complexes, the semi-empirical method PM6 was used. The solvent effect has been taken into account by using implicit modelling and the conductor-like polarizable continuum model.

Six density functionals (M11, M11L, MN12L, MN12SX, N12, and N12SX) in connection with the Def2TZVP basis set and the SMD solvation model (water as a solvent) have been assessed for the calculation of the molecular structure and properties of several peptides with the general formulaAc-Lys-(Ala)n-Lys-NH2,withn=0to5 [...]