Benzopyrazine-Based Small Molecule Inhibitors As Trypanocidal and Leishmanicidal Agents: Green Synthesis, In Vitro, and In Silico Evaluations

World Health Organization (WHO) identified twenty tropical disease categories as neglected tropical diseases (NTDs)1. Chagas’ disease (also known as American trypanosomiasis) and leishmaniasis are two major classes of NTDs. The total number of mortality, morbidity, and disability attributed each year due to these two categories of diseases in magnitudes is much higher than the so-called elite diseases like cancer, diabetes, AIDS, cardiovascular and neurodegenerative diseases. Impoverished communities around the world are the major victim of NTDs. The development of new and novel drugs in the battle against Chagas’ disease and leishmaniasis is highly anticipated. An easy and straightforward on-water green access to synthesize benzopyrazines is reported. This ultrasound-assisted procedure does not require any catalyst/support/additive/hazardous solvents and maintains a high atom economy. A series of eleven benzopyrazines has been synthesized, and most of the synthesized compounds possess the drug-likeness following Lipinski’s “Rule of 5”. Benzopyrazines 3 and 4 demonstrated moderate leishmanicidal activity against L. mexicana (M378) strain. The selective lead compound 1 showed good leishmanicidal, and trypanocidal activities (in vitro) against both L. mexicana (M378) and T. cruzi (NINOA) strains compared to the standard controls. The in vitro trypanocidal and leishmanicidal activities of the lead compound 1 have been validated by molecular docking studies against four biomolecular drug targets viz. T. cruzi histidyl-tRNA synthetase, T. cruzi trans-sialidase, leishmanial rRNA A-site, and leishmania major N-myristoyl transferase

The wound healing action of a cream latex formulation of Jatropha gaumeri Greenm. in a pre-clinical model

Background and Aim: Jatropha gaumeri Greenm. is commonly used to treat mouth blisters and skin rashes, its latex has analgesic and anti-inflammatory activity on buccal ulcer. This study aimed to demonstrate the wound healing activity of a cream formulation of Jatropha gaumeri Greenm. latex in a murine model, provide a histological assessment of its scarring effects, and identify the family of phytochemicals involved in these effects. Materials and Methods: Latex was obtained from the cut stalk leaves and young stems of J. gaumeri and stored in sterile tubes with protection from light. Chloroform, ethyl acetate, and aqueous fractions of the latex were obtained. Fifty male Balb/c mice aged 10-12 weeks were divided into 10 groups of five mice: Group 1 corresponded to healthy mice with wounds; Group 2 corresponded to mice with wounds and treated with A-Derma®; and from Group 3 to group 10 corresponded to mice treated with a different latex fraction. A circular skin wound of about 1 cm was made on the paravertebral region of each mouse under anesthetized and aseptic conditions. The wounds were topically treated every 24 h with the respective extracts for 22 days, after which skin tissue specimens were obtained and stained with hematoxylin-eosin and Masson's trichrome. The efficiency of healing was measured by quantifying the tensile strength of the scars. The phytochemicals in the latex were elucidated using thin chromatography. Results: The aqueous latex fraction produced the best wound healing activity and was superior to the positive control. Reepithelialization at the histological level resulted in tissue that resembled healthy skin in terms of the appearance of collagen, the regeneration of hair follicles, and cellularity of the dermis, which showed organized epithelialization. A wound healing efficacy of 97% was observed, and it seems that alkaloids were the phytochemicals mostly likely responsible for these effects. Conclusion: J. gaumeri latex exhibited wound healing activity, possibly mediated by phytochemicals such as alkaloids in the aqueous fraction

Microorganisms as a Potential Source of Molecules to Control Trypanosomatid Diseases

Trypanosomatids are the causative agents of leishmaniasis and trypanosomiasis, which affect about 20 million people in the world’s poorest countries, leading to 95,000 deaths per year. They are often associated with malnutrition, weak immune systems, low quality housing, and population migration. They are generally recognized as neglected tropical diseases. New drugs against these parasitic protozoa are urgently needed to counteract drug resistance, toxicity, and the high cost of commercially available drugs. Microbial bioprospecting for new molecules may play a crucial role in developing a new generation of antiparasitic drugs. This article reviews the current state of the available literature on chemically defined metabolites of microbial origin that have demonstrated antitrypanosomatid activity. In this review, bacterial and fungal metabolites are presented; they originate from a range of microorganisms, including cyanobacteria, heterotrophic bacteria, and filamentous fungi. We hope to provide a useful overview for future research to identify hits that may become the lead compounds needed to accelerate the discovery of new drugs against trypanosomatids

Benzochromenes from the roots of Bourreria pulchra

Two new benzochromenes, (6,6-dimethyl-2-methoxy-6H-benzo[c]chromen-9-yl)methanol (1), and 2-methoxy-6,6-dimethyl-6H-benzo[c]chromen-9-carbaldehyde (2), together with several already known metabolites, were isolated from the root extract of Bourreria pulchra (Boraginaceae). The structures of 1 and 2 were established on the basis of their spectroscopic data. Both were assayed for in vitro antiprotozoan activity, and especially 1 was found to possess significant activity against Leishmania mexicana and Trypanosoma cruzi parasites (IC50 4.6 mu g/mL and 7.5 mu g/mL, respectively). (C) 2009 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved

Trinorsesquiterpenoids from the Root Extract of Pentalinon andrieuxii

Two unusual trinorsesquiterpenoids, urechitols A (1) and B (2), were isolated from the root extract of Pentalinon andrieuxii, a plant used commonly in Yucatecan traditional medicine to treat leishmaniasis. The structures of I and 2 were identified by interpretation of their spectroscopic data and chemical correlation reactions. The relative stereochemistry of I was confirmed through an X-ray crystallographic study

Antimicrobial engineered nanoparticles in the built cultural heritage context and their ecotoxicological impact on animals and plants: a brief review

Abstract Nanoparticles (NPs) of metal oxides, sometimes referred to as engineered nanoparticles have been used to protect building surfaces against biofilm formation for many years, but their history in the Cultural Heritage world is rather short. Their first reported use was in 2010. Thereafter, a wealth of reports can be found in the literature, with Ti, Ag and Zn oxides being the major protagonists. As with all surface treatments, NPs can be leached into the surrounding environment, leading to potential ecotoxicity in soil and water and associated biota. Dissolution into metal ions is usually stated to be the main mode of toxic action and the toxic effects, when determined in the marine environment, decrease in the order Au > Zn > Ag > Cu > Ti > C60, but direct action of NPs cannot be ruled out. Although ecotoxicity has been assessed by a variety of techniques, it is important that a suitable standard test be developed and the European Unions’s Biocidal Product Registration group is working on this, as well as a standard test for antimicrobial efficacy to determine their impact on ecological processes of surrounding non-target organisms and their transformation products under realistic scenarios

Bioweathering potential of cultivable fungi associated with semi-arid surface microhabitats of Mayan buildings

Soil and rock surfaces support microbial communities involved in mineral weathering processes. Using selective isolation, fungi were obtained from limestone surfaces of Mayan monuments in the semi-arid climate at Yucatan, Mexico. A total of 101 isolates representing 53 different taxa were studied. Common fungi such as Fusarium, Pestalotiopsis, Trichoderma and Penicillium were associated with surfaces and were, probably derived from airborne spores. In contrast, unusual fungi such as Rosellinia, Annulohypoxylon, and Xylaria were predominantly identified from mycelium particles of biofilm biomass. Simulating oligotrophic conditions, agar amended with CaCO3 was inoculated with fungi to test for carbonate activity. A substantial proportion of fungi, in particular those isolated from mycelium (59%), were capable of solubilizing calcium by means of organic acid release, notably oxalic acid as evidenced by ion chromatography. Contrary to our hypothesis, nutrient level was not a variable influencing the CaCO3 solubilization ability among isolates. Particularly active fungi (Annulohypoxylon stygium, Penicillium oxalicum and Rosellinia sp.) were selected as models for bioweathering experiments with limestone-containing mesocosms to identify if other mineral phases, in addition to oxalates, were linked to bioweathering processes. Fungal biofilms were seen heavily covering the stone surface, while a biomineralized front was also observed at the stone-biofilm interface, where network of hyphae and mycogenic crystals was observed. X-ray diffraction analysis (XRD) identified calcite as the main phase, along with whewellite and wedellite. In addition, lower levels of citrate were detected by Attenuated Total Reflectance-Fourier-Transform Infrared Spectroscopy (ATR-FTIR). Overall, our results suggest that a diverse fungal community is associated with limestone surfaces insemi-arid climates. A subset of this community is geochemically active, excreting organic acids under quasi-oligotrophic conditions, suggesting that the high metabolic cost of exuding organic acids beneficial under nutrient limitation. Oxalic acid release may deteriorate or stabilize limestone surfaces, depending on microclimatic dynamics

Emulsifying Activity and Stability of a Non-Toxic Bioemulsifier Synthesized by Microbacterium sp MC3B-10

A previously reported bacterial bioemulsifier, here termed microbactan, was further analyzed to characterize its lipid component, molecular weight, ionic character and toxicity, along with its bioemulsifying potential for hydrophobic substrates at a range of temperatures, salinities and pH values. Analyses showed that microbactan is a high molecular weight (700 kDa), non-ionic molecule. Gas chromatography of the lipid fraction revealed the presence of palmitic, stearic, and oleic acids; thus microbactan may be considered a glycolipoprotein. Microbactan emulsified aromatic hydrocarbons and oils to various extents; the highest emulsification index was recorded against motor oil (96%). The stability of the microbactan-motor oil emulsion model reached its highest level (94%) at 50 degrees C, pH 10 and 3.5% NaCl content. It was not toxic to Artemia salina nauplii. Microbactan is, therefore, a non-toxic and non-ionic bioemulsifier of high molecular weight with affinity for a range of oily substrates. Comparative phylogenetic assessment of the 16S rDNA gene of Microbacterium sp. MC3B-10 with genes derived from other marine Microbacterium species suggested that this genus is well represented in coastal zones. The chemical nature and stability of the bioemulsifier suggest its potential application in bioremediation of marine environments and in cosmetics