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: We have synthesized twenty-three 1,4-dihydropyridine derivatives (1,4-DHPs) by using a microwave-assisted one-pot multicomponent Hantzsch reaction and evaluated their antibacterial activity against a representative panel of cariogenic bacteria and their in vitro antileishmanial activity against Leishmania (L.) amazonensis promastigotes and amastigotes. Thirteen compounds were moderately active against Streptococcus sanguinis, Streptococcus mitis, and Lactobacillus paracasei. Compound 22 (diethyl 4-(3-methoxy-4-hydroxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) displayed moderate antibacterial activity against S. mitis and S. sanguinis, with a Minimum Inhibitory Concentration (MIC) of 500 µg/mL); compounds 8 (ethyl 2,7,7-trimethyl-4-(3-chlorophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) and 10 (ethyl 2,7,7-trimethyl-4-(3-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) were moderately active against S. sanguinis (MIC = 500 µg/mL) and very active against L. amazonensis promastigotes (IC50 = 43.08 and 34.28 µM, respectively). Among the eight 1,4-DHPs that were active (IC50 < 50 µM) against L. amazonensis promastigotes, compound 13 (ethyl 2,7,7-trimethyl-4-(3,4,5-trimethoxyphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) was the most active (IC50 = 24.62 µM) and had a Selectivity Index (SI) higher than 4 compared to GM07492A cells. On the other hand, compound 9 (ethyl 2,7,7-trimethyl-4-(2-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) was the most active against L. amazonensis amastigotes (IC50 = 16.27 µM and SI = 6.1) after 24 h of treatment. Based on our results, asymmetric 1,4-DHPs derived from dimedone exhibit antileishmanial potential.

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Artepillin C, drupanin, and plicatin B are prenylated phenylpropanoids that naturally occur in Brazilian green propolis. In this study, these compounds and eleven of their derivatives were synthesized and evaluated for their in vitro antimicrobial activity against a representative panel of oral bacteria in terms of their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. Plicatin B (2) and its hydrogenated derivative 8 (2',3',7,8-tetrahydro-plicatin B) were the most active compounds. Plicatin B (2) displayed strong activity against all the bacteria tested, with an MIC of 31.2 µg/mL against Streptococcus mutans, S. sanguinis, and S. mitis. On the other hand, compound 8 displayed strong activity against S. mutans, S. salivarius, S. sobrinus, Lactobacillus paracasei (MIC = 62.5 µg/mL), and S. mitis (MIC = 31.2 µg/mL), as well as moderate activity against Enterococcus faecalis and S. sanguinis (MIC = 125 µg/mL). Compounds 2 and 8 displayed bactericidal effects (MBC: MIC ≤ 4) against all the tested bacteria. In silico studies showed that the complexes formed by compounds 2 and 8 with the S. mitis, S. sanguinis, and S. mutans targets (3LE0, 4N82, and 3AIC, respectively) had energy score values similar to those of the native S. mitis, S. sanguinis, and S. mutans ligands due to the formation of strong hydrogen bonds. Moreover, all the estimated physicochemical parameters satisfied the drug-likeness criteria without violating the Lipinski, Veber, and Egan rules, so these compounds are not expected to cause problems with oral bioavailability and pharmacokinetics. Compounds 2 and 8 also had suitable ADMET parameters, as the online server pkCSM calculates. These results make compounds 2 and 8 good candidates as antibacterial agents against oral bacteria.

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Callistemon viminalis has been widely known due to its therapeutic properties. Tuberculosis is a deadly infectious disease caused predominantly by Mycobacterium tuberculosis. Other respiratory diseases may also be caused by nontuberculous mycobacteria. Malassezia furfur causes dermal inflammation and tissue damage. This study aimed to evaluate in vitro inhibitory effects of essential oils (EOs) from C. viminalis leaves (EO-CL) and flowers (EO-CF) against M. tuberculosis, Mycobacterium kansasii, Mycobacterium avium and M. furfur strains. Their cytotoxic activity was evaluated by the brine shrimp assay. Resulting MIC values of all EOs under study were promising since they ranged from 50 to 100 µg/mL. Both EO-CL and EO-CF showed nontoxicity against Artemia salina by the brine shrimp assay (LC50 > 1000 µg/mL). GC-FID and GC-MS analyses showed that 1,8-cineole was the major component of both EOs. These results revealed the promising potential of EO-CL and EO-CF to develop new antibacterial and antifungal drugs.

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This study reports on the chemical composition and antileishmanial and anticandidal activities of volatile oils (VOs) of Schinus molle dried leaves (SM), Cinnamomum cassia branch bark (CC) and their blends. Major constituents of SM were spathulenol (26.93 %), ß-caryophyllene (19.90 %), and caryophyllene oxide (12.69 %), whereas (E)-cinnamaldehyde (60.11 %), cinnamyl acetate (20.90 %) and cis-2-methoxycinnamic acid (10.37 %) were predominant in CC. SM (IC50=21.45 µg/mL) and CC (IC50=23.27 µg/mL) displayed good activity against L. amazonensis promastigotes, besides having good or moderate activity against nine Candida strains, with Minimum Inhibitory Concentration (MIC) values ranging from 31.25 to 250 µg/mL. While the three SM and CC blends were not more active than the VOs tested individually, they exhibited remarkably high antileishmanial activity, with IC50 values ranging between 3.12 and 7.04 µg/mL, which is very similar to the IC50 of amphotericin B (positive control).

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We have investigated the gas-phase fragmentation reactions of 11 synthetic 4-aryl-3,4-dihydrocoumarins by electrospray ionization tandem mass spectrometry (ESI-MS/MS) on a quadrupole-time-of flight (Q-TOF) hybrid mass spectrometer. We have also estimated thermochemical data for the protonated coumarins (precursor ion A) and product ion structures by computational chemistry at a B3LYP level of theory to establish the ion structures and to rationalize the fragmentation pathways. The most abundant ions in the product ion spectra of coumarins 1-11 resulted from C8H8O2, CO2, C4H4O3, C8H10O3, C8H8O2, and CH3OH eliminations through retro-Diels-Alder (RDA) reactions, remote hydrogen rearrangements (ß-eliminations), and ß-lactone ring contraction. Although the investigated coumarins shared most of the fragmentation pathways, formation of a benzylic product ion and its corresponding tropylium ion was diagnostic of the substituents at ring C. The thermochemical data revealed that the nature and position of the substituents at ring C played a key role in the formation of this product ion and determined its relative intensity in the product ion spectrum. The results of this study contribute to knowledge of the gas-phase ion chemistry of this important class of organic compounds.

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Natural Rubber Latex (NRL) has shown to be a promising biomaterial for use as a drug delivery system to release various bioactive compounds. It is cost-effective, easy to handle, biocompatible, and exhibits pro-angiogenic and pro-healing properties for both soft and hard tissues. NRL releases compounds following burst and sustained release kinetics, exhibiting first-order release kinetics. Moreover, its pore density can be adjusted for tailored kinetics profiles. In addition, biotechnological applications of NRL in amblyopia, smart mattresses, and neovaginoplasty have demonstrated success. This comprehensive review explores NRL's diverse applications in biotechnology and biomedicine, addressing challenges in translating research into clinical practice. Organized into eight sections, the review emphasizes NRL's potential in wound healing, drug delivery, and metallic nanoparticle synthesis. It also addresses the challenges in enhancing NRL's physical properties and discusses its interactions with the human immune system. Furthermore, examines NRL's potential in creating wearable medical devices and biosensors for neurological disorders. To fully explore NRL's potential in addressing important medical conditions, we emphasize throughout this review the importance of interdisciplinary research and collaboration. In conclusion, this review advances our understanding of NRL's role in biomedical and biotechnological applications, offering insights into its diverse applications and promising opportunities for future development.

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We have evaluated eight p-coumaric acid prenylated derivatives in vitro for their antileishmanial activity against Leishmania amazonensis promastigotes and their antischistosomal activity against Schistosoma mansoni adult worms. Compound 7 ((E)-3,4-diprenyl-4-isoprenyloxycinnamic alcohol) was the most active against L. amazonensis (IC50=45.92 µM) and S. mansoni (IC50=64.25 µM). Data indicated that the number of prenyl groups, the presence of hydroxyl at C9, and a single bond between C7 and C8 are important structural features for the antileishmanial activity of p-coumaric acid prenylated derivatives.

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Neglected tropical diseases are significant causes of death and temporary or permanent disability for millions living in developing countries. Unfortunately, there is no effective treatment for these diseases. Thus, this work aimed to conduct a chemical analysis using HPLC/UV and GC/MS to identify the major constituents of the hydroalcoholic extracts of Capsicum frutescens and Capsicum baccatum fruits, evaluating these extracts and their constituents' schistosomicidal, leishmanicidal and trypanocidal activities. The results obtained for the extracts of C. frutescens are better when compared to those obtained for C. baccatum, which can be related to the different concentrations of capsaicin (1) present in the extracts. The lysis of trypomastigote forms results for capsaicin (1) led to a significant value of IC50 = 6.23 µM. Thus, the results point to capsaicin (1) as a possible active constituent in these extracts.

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Advances and the discovery of new biomaterials have opened new frontiers in regenerative medicine. These biomaterials play a key role in current medicine by improving the life quality or even saving the lives of millions of people. Since the 2000s, Natural Rubber Latex (NRL) has been employed as wound dressings, mechanical barrier for Guided Bone Regeneration (GBR), matrix for drug delivery, and grafting. NRL is a natural polymer that can stimulate cell proliferation, neoangiogenesis, and extracellular matrix (ECM) formation. Furthermore, it is well established that proteins and other biologically active molecules present in the Natural Latex Serum (NLS) are responsible for the biological properties of NRL. NLS can be obtained from NRL by three main methods, namely (i) Centrifugation (fractionation of NRL in distinct fractions), (ii) Coagulation and sedimentation (coagulating NRL to separate the NLS from rubber particles), and (iii) Alternative extraction process (elution from NRL membrane). In this review, the chemical composition, physicochemical properties, toxicity, and other biological information such as osteogenesis, vasculogenesis, adhesion, proliferation, antimicrobial behavior, and antitumoral activity of NLS, as well as some of its medical instruments and devices are discussed. The progress in NLS applications in the biomedical field, more specifically in cell cultures, alternative animals, regular animals, and clinical trials are also discussed. An overview of the challenges and future directions of the applications of NLS and its derivatives in tissue engineering for hard and soft tissue regeneration is also given.

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Pterodon pubescens Benth is a Brazilian medicinal plant (sucupira, in Brazilian Portuguese). This paper aims to determine the volatile composition and antibacterial activities of hexane extract from P. pubescens seeds (HE-PP). Antibacterial activities were screened by the microdilution broth method in 96-well culture plates and MIC values were expressed as µg/mL. HE-PP was active against several oral bacteria whose MIC values ranged between 12.5 µg/mL and 50 µg/mL and against three mycobacterial strains (MIC = 125 µg/mL and 500 µg/mL). In addition, HE-PP was active against Xanthomonas citri strain (MIC = 100 µg/mL). Cytotoxic activity of the extract was evaluated in human tumour and non-tumour cell lines. HE-PP showed selective cytotoxicity to cervical adenocarcinoma (HeLa cells - IC50 = 53.47 µg/mL). Its major constituents were identified by GC-MS and GC-FID: E-caryophyllene, vouacapane, E-geranylgeraniol and dehydroabietol. Results reinforce the biological potential of HE-PP against a broad spectrum of pathogenic and phytopathogenic bacteria.

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Casearia species are found in the America, Africa, Asia, and Australia and present pharmacological activities, besides their traditional uses. Here, we reviewed the chemical composition, content, pharmacological activities, and toxicity of the essential oils (EOs) from Casearia species. The EO physical parameters and leaf botanical characteristics were also described. The bioactivities of the EOs from the leaves and their components include cytotoxicity, anti-inflammatory, antiulcer, antimicrobial, antidiabetic, antioxidant, antifungal, and antiviral activities. The main components associated with these activities are the α-zingiberene, (E)-caryophyllene, germacrene D, bicyclogermacrene, spathulenol, α-humulene, ß-acoradiene, and δ-cadinene. Data on the toxicity of these EOs are scarce in the literature. Casearia sylvestris Sw. is the most studied species, presenting more significant pharmacological potential. The chemical variability of EOs components was also investigated for this species. Caseria EOs have relevant pharmacological potential and must be further investigated and exploited.

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Applying elicitors in plants growing under natural conditions change the metabolic content of volatile compounds extracted from their tissues. Here, we have investigated how abiotic elicitors influence the volatile composition of the ethyl acetate extract of Anacardium othonianum seedlings propagated in vitro and ex-vitro cultures. Abiotic factors such as salicylic acid, silver nitrate, light quality, and cultivation mode affected the composition of volatile compounds in ethyl acetate extract of A. othonianum leaves seedlings. GC/MS analysis demonstrated that α-tocopherol was the main metabolite in cultures added with chemical elicitors, reaching 22.48 ± 4.06% in the case of 30 µM salicylic acid. Higher concentrations of salicylic acid decreased the amount of α-tocopherol. The addition of AgNO3 had a linear effect on α-tocopherol. Thus, the production of this metabolite indicates that salicylic acid and AgNO3 elicitors positively affect α-tocopherol production at specific concentrations helping to understand how plant culture can be better manipulated.

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Chagas disease is a neglected tropical disease that affects more than 8 million people. Although there are therapies against this disease, the search for new drugs is important because the current treatments show limited effectiveness and high toxicity. In this work, eighteen dihydrobenzofuran-type neolignans (DBNs) and two benzofuran-type neolignans (BNs) were synthesized and evaluated against amastigote forms of two Trypanosoma cruzi strains. The in vitro cytotoxicity and hemolytic activity of the most active compounds were also evaluated and their relationships with T. cruzi tubulin DBNs were investigated by an in silico approach. Four DBNs demonstrated activity against the T. cruzi Tulahuen lac-Z strain (IC50 from 7.96 to 21.12 µM), and DBN 1 exhibited the highest activity against the amastigote forms of the T. cruzi Y strain (IC50 3.26 µM). Compounds 1-4 showed CC50 values higher than antitrypanosomal activities, except for DBN 3. All DBNs with antitrypanosomal activity demonstrated CH50 higher than 100 µM. The in silico results indicated that DBNs 1, 2, and 4 are capable of destabilizing the dynamics of the tubulin-microtubule from the vinca site. These compounds displayed promising in vitro activity against T. cruzi, especially compound 1, and can be considered molecular prototypes for the development of new antiparasitic drugs.

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The growth of the world population has prompted research to investigate new food/feed alternatives. Hemp-based products can be considered excellent candidates. Hemp (Cannabis sativa L.) is an environmentally sustainable plant widespread worldwide. Following the reintroduction of its cultivation, hemp is attracting interest, especially in the food/feed industry. To date, scientific research has mainly focused on its nutritional aspect. Therefore, the aim of the work was also to investigate the functional profile (total phenolic content (TPC) and antioxidant activity (Ferric- reducing antioxidant power (FRAP) and 2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS)) of hemp-based products (hempseeds (HSs), flowers, and HS protein extract), following methanol extraction and in vitro digestion, to study the behaviour of the molecules involved. The results show an interesting nutritional value, even when compared to matrices used in the food/feed industry, such as soy and flaxseeds. The functional profile revealed a very interesting TPC following methanol extraction for HSs, flowers, and HS protein extract, respectively, (550.3 ± 28.27; 2982.8 ± 167.78; and 568.9 ± 34.18 mg Tannic Acid Equivalent (TAE)/100 g). This trend was also confirmed for FRAP (50.9 ± 4.30; 123.6 ± 8.08; and 29.73 ± 1.32 mg Ascorbic Acid Equivalent (AAE)/100 g), recording values similar/higher than soy protein extract and flaxseeds (17.4 ± 1.55; and 10.4 ± 0.44 mg AAE/100 g). The results were also maintained following physiological digestion. These results, although promising, need further investigation, confirming what has been observed with different antioxidant activity assays and identifying individual molecules involved in functional pathways. This information will be necessary to gain a better understanding of the functional characteristics of these matrices for use in food/feed formulations.

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Trypanosoma brucei is a protozoan parasite that causes Human African Trypanosomiasis (HAT), a neglected tropical disease (NTD) that is endemic in 36 countries in sub-Saharan Africa. Only a handful drugs are available for treatment, and these have limitations, including toxicity and drug resistance. Using the natural product, curcumin, as a starting point, several curcuminoids and related analogs were evaluated against bloodstream forms of T. b. brucei. A particular subset of dibenzylideneacetone (DBA) compounds exhibited potent in vitro antitrypanosomal activity with sub-micromolar EC50 values. A structure-activity relationship study including 26 DBA analogs was initiated, and several compounds exhibited EC50 values as low as 200 nM. Cytotoxicity counter screens in HEK293 cells identified several compounds having selectivity indices above 10. These data suggest that DBAs offer starting points for a new small molecule therapy of HAT.

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This study aimed to investigate the chemical composition as well as the antibacterial, antiparasitic, and cytotoxic potentialities of the Brazilian Chrysopogon zizanioides root essential oil (CZ-EO) In addition, CZ-EO cytotoxicity to LLCMK2 adherent epithelial cells was assessed. The major compounds identified in CZ-EO were khusimol (30.0 ± 0.3%), ß-eudesmol (10.8 ± 0.3%), α-muurolene (6.0 ± 0.1%), and patchouli alcohol (5.6 ± 0.2%). CZ-EO displayed optimal antibacterial activity against Prevotella nigrescens, Fusobacterium nucleatum, Prevotella melaninogenica, and Aggregatibacter actinomycetemcomitans, with Minimum Inhibitory Concentration (MIC) values between 22 and 62.5 µg/mL and Minimum Bactericidal Concentration (MBC) values between 22 and 400 µg/mL. CZ-EO was highly active against the L. amazonensis promastigote and amastigote forms (IC50 = 7.20 and 16.21 µg/mL, respectively) and the T. cruzi trypomastigote form (IC50 = 11.2 µg/mL). Moreover, CZ-EO showed moderate cytotoxicity to LLCMK2 cells, with CC50 = 565.4 µg/mL. These results revealed an interesting in vitro selectivity of CZ-EO toward the L. amazonensis promastigote and amastigote forms (Selectivity Index, SI = 78.5 and 34.8, respectively) and the T. cruzi trypomastigote form (SI = 50.5) compared to LLCMK2 cells. These results showed the promising potential of CZ-EO for developing new antimicrobial, antileishmanial, and antitrypanosomal drugs.

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The current trend toward using natural food additives, cosmetics, and medicines has motivated industries to substitute synthetic compounds for natural products. Essential oils (EOs) from medicinal plants are a well-known source of chemical compounds that display several interesting biological activities, including antimicrobial action. In this study, we investigated the antibacterial activity of EOs extracted from three Piperaceae species collected in the Brazilian Amazon region against a representative panel of cariogenic bacteria. The minimum inhibitory concentration (MIC) of the essential oils extracted from Peperomia pellucida (PP-EO), Piper marginatum (PM-EO), and Piper callosum (PC-EO) was determined against Streptococcus mutans, S. mitis, S. sanguinis, S. salivarius, S. sobrinus, Enterococcus faecalis, and Lactobacillus casei by using the microplate microdilution method. PM-EO, PC-EO, and PP-EO displayed antibacterial activity against all the tested cariogenic bacteria. PM-EO displayed the best inhibitory activity, with MIC values ranging from 50 to 500 µg/mL. The lowest MIC values were obtained for PM-EO against S. mitis (MIC = 75 µg/mL), Lactobacillus casei (MIC = 50 µg/mL), and S. mutans (MIC = 50 µg/mL). Gas chromatography mass spectrometry (GC-MS) analysis allowed the chemical composition of all the EOs to be identified. The main constituents of PM-EO, PC-EO, and PP-EO were 3,4-(methylenedioxy)propiophenone, α-pinene, and dillapiole, respectively. Finally, the compounds that were exclusively detected in PM-EO are highlighted. Our results suggest that PM-EO may be used in products for treating dental caries and periodontal diseases.

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This article aims to investigate volatile constituents and antiacetylcholinesterase, antileishmanial and antiproliferative activities of hexane extracts from Capsicum chinense fruit (unripe bode pepper 'HE-UB' and ripe little beak pepper 'HE-RB'). HE-UB and HE-RB were screened by the microplate assay method to determine their antiacetylcholinesterase activity. Both exhibited inhibitory potential, i. e., IC50 = 41.5 and 20.3 µg/mL, respectively. HE-UB (IC50 = 67.19 µg/mL) and HE-RB (IC50 = 38.16 µg/mL) exhibited antileishmanial activity against promastigote forms of Leishmania (Leishmania) amazonensis. In addition, HE-UB and HE-RB demonstrated cytotoxic activity against different human tumor cell lines with IC50 ranging from 325.40 to 425.0 µg/mL. Both GC-FID and GC-MS analyses revealed that the major component in both extracts was E-caryophyllene. In short, HE-RB was more satisfactory than HE-UB in all in vitro activities under evaluation. These findings may be used as initial data for further studies of Capsicum species.

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This updated review article covers the literature between 2011 and 2021 on the antibacterial activity of EOs against the main bacteria that cause caries and periodontal diseases. The criteria to classify the in vitro antibacterial activity of EOs is updated and the most promising results are addressed.

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This review article covers literature on the antischistosomal activity of essential oils (EOs) between 2011 and 2021. Criteria for classifying results from in vitro schistosomicidal assays are proposed for the first time. Parameters to evaluate the in vitro antischistosomal potential of EOs other than their ability to cause the death of Schistosoma mansoni adult worms (e. g., couple separation, egg laying, and egg development inhibition) are also addressed and discussed.

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