Leishmaniasis is endemic in at least 98 countries. Due to the high toxicity and resistance associated with the drugs, we chose lignans as an alternative, due to their favorable properties of absorption, distribution, metabolism, excretion, and toxicity (ADMET). To investigate their leishmanicidal potential, the biological activities of a set of 160 lignans were predicted using predictive models that were built using data for Leishmania major and L. (Viannia) braziliensis. A combined analysis, based on ligand and structure, and several other computational approaches were used. The results showed that the combined analysis was able to select 11 lignans with potential activity against L. major and 21 lignans against L. braziliensis, with multitargeting effects and low or no toxicity. Of these compounds, four were isolated from the species Justicia aequilabris (Nees) Lindau. All of the identified compounds were able to inhibit the growth of L. braziliensis promastigotes, with the most active compound, (159) epipinoresinol-4-O-β-d-glucopyranoside, presenting an IC50 value of 5.39 µM and IC50 value of 36.51 µM for L. major. Our findings indicated the potential of computer-aided drug design and development and demonstrated that lignans represent promising prototype compounds for the development of multitarget drugs against leishmaniasis.

Alzheimer’s disease (AD) is characterized by the progressive disturbance in cognition and affects approximately 36 million people, worldwide. However, the drugs used to treat this disease are only moderately effective and do not alter the course of the neurodegenerative process. This is because the pathogenesis of AD is mainly associated with oxidative stress, and current drugs only target two enzymes involved in neurotransmission. Therefore, the present study sought to identify potential multitarget compounds for enzymes that are directly or indirectly involved in the oxidative pathway, with minimal side effects, for AD treatment. A set of 159 lignans were submitted to studies of QSAR and molecular docking. A combined analysis was performed, based on ligand and structure, followed by the prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. The results showed that the combined analysis was able to select 139 potentially active and multitarget lignans targeting two or more enzymes, among them are c-Jun N-terminal kinase 3 (JNK-3), protein tyrosine phosphatase 1B (PTP1B), nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), NADPH quinone oxidoreductase 1 (NQO1), phosphodiesterase 5 (PDE5), nuclear factor erythroid 2-related factor 2 (Nrf2), cycloxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). The authors conclude that compounds (06) austrobailignan 6, (11) anolignan c, (19) 7-epi-virolin, (64) 6-[(2R,3R,4R,5R)-3,4-dimethyl-5-(3,4,5-trimethoxyphenyl)oxolan-2-yl]-4-methoxy-1,3-benzodioxole, (116) ococymosin, and (135) mappiodoinin b have probabilities that confer neuroprotection and antioxidant activity and represent potential alternative AD treatment drugs or prototypes for the development of new drugs with anti-AD properties.

Background: Tuberculosis is a disease with high incidence and high mortality rate, especially in Brazil. Although there are several medications available for treatment, in cases of resistance, there is a need to use more than one medication. Objective: Therefore, cases of toxicity increase and reports of resistance have been worrying the population. In addition, some medications have a short period of effectiveness. To achieve the goal, ligand-based and structure-based approaches were used. Method: Thus, in an attempt to discover potent inhibitors against Mycobacterium tuberculosis enzymes, we sought to identify natural products with high therapeutic potential for the treatment of Tuberculosis through QSAR, Molecular Modeling and ADMET studies. Results: The results showed that the models generated from two sets of molecules with known activity against M. tuberculosis enzymes InhA and PS were able to select 11 and 8 compounds respectively, between Lignans and Neolignans with 50 to 60% activity probability. In addition, molecular docking contributed to confirm the mechanism of action of compounds and increase the accuracy of methodologies. All molecules showed higher binding energy values for the drug Isoniazid. We conclude that compounds 33, 34, 110, 114, 133 are promising for InhA target and compounds 07, 08, 19, 21, 42, 48, 75 and 141 for target PS. In addition, most molecules did not show any toxicity according to the evaluated parameters. Conclusions: Therefore, Lignans and Neolignans may be an alternative for the treatment of Tuberculosis.

The goal of this study was to perform in silico identification of bioinsecticidal potential of 42 monoterpenes against Drosophila melanogaster and Reticulitermes chinensis Snyder. Quantitative structure−activity relationship (QSAR) modeling was performed for both organisms, while docking and molecular dynamics were used only for Drosophila melanogaster. Neryl acetate has the lowest interaction energy (−87 kcal/mol) against active site of acetylcholinesterase, which is comparable to the ones of methiocarb and pirimicarb (−90 kcal/mol) and reported PDB binder 9-(3-iodobenzylamino)-1,2,3,4-tetrahydroacridine (−112.67 kcal/mol). Interaction stability was verified by molecular dynamics simulations and showed that the stability of ACHE active site complexes with three selected terpenes is comparable to the one of the pirimicarb and methiocarb. Overall, our results suggest that pulegone, citronellal, carvacrol, linalyl acetate, neryl acetate, citronellyl acetate, and geranyl acetate may be considered as a potential pesticide candidates.

Background: The emergence of a new coronavirus (CoV), named 2019-nCoV, in an outbreak located in the city of Wuhan, China, has resulted in the death more than 3,400 people this year alone and has caused worldwide alarm, particularly following previous CoV epidemics, including the Severe Acute Respiratory Syndrome (SARS) in 2003 and the Middle East Respiratory Syndrome (MERS) in 2012. No treatment currently exists for infections caused by CoVs; however, some natural products may represent potential treatment resources, such as those that contain diterpenes. Objective: This study aimed to use computational methods to perform a virtual screen (VS) of candidate diterpenes with the potential to act as CoV inhibitors. Methods: 1,955 diterpenes, derived from a Nepetoideae subfamily (Lamiaceae), were selected using the SistematX tool (https://sistematx.ufpb.br), which were used to make predictions. From the ChEMBL database, 3 sets of chemical structures were selected for the construction of predictive models. Results: The chemical structures of molecules with known activity against SARS CoV, two of which were tested for activity against specific viral proteins and one of which was tested for activity against the virus itself, were classified according to their pIC50 values [-log IC50 (mol/l)]. Conclusion: The consensus analysis approach, combining both ligand- and structure-based VSs, 19 compounds were selected as potential CoV inhibitors, including isotanshinone IIA (01), tanshinlactone (02), isocryptotanshinone (03), and tanshinketolactone (04), which did not present toxicity within the evaluated parameters.