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Vitiligo is a chronic disease of unknown etiology that causes progressive cutaneous depigmentation. Current pharmacological treatments have limited success and present significant risks. Many efforts have been made in recent years to explore new anti-vitiligo therapeutic strategies, including herbal-based therapies. The objective of the present review is to provide an updated overview on the most frequently used medicinal plants in the treatment of vitiligo. A bibliographical search was carried out in scientific databases Pubmed, Scifinder, Scopus, Google Scholar, and Medline up to October 2021 using the descriptors vitiligo, herbal, medicinal plants, and alternative therapies. In our search, the highest number of published studies comprise plants commonly used in traditional herbal medicine, highlighting the usefulness of ethnopharmacology in the discovery of new therapeutic agents. The review outlines current understanding and provides an insight into the role of psoralens and khellin (photosensitizing agents obtained from plants such as Cullen corylifolium or Ammi visnaga ). The paper also describes other traditional herbs such as Ginkgo biloba, Phlebodium aureum, Piper nigrum, Picrorhiza kurroa, and Baccharoides anthelmintica that can likewise act as potential therapeutical agents. Based on our findings, photosensitizing agents in combination with phototherapy, the association of oral Phebodium aureum with phototherapies as well as oral G. biloba in monotherapy showed greater scientific evidence as therapeutic options. The research results emphasize that further investigation in this area is merited. More long-term follow up clinical trials and higher quality randomized trials are needed., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The incidence and prevalence of age-related neurodegenerative dementias have been increasing. There is no curative therapy and conventional drug treatment can cause problems for patients. Medicinal plants traditionally used for problems associated with ageing are emerging as a therapeutic resource. The main aim is to give a proposal for use and future research based on scientific knowledge and tradition. A literature search was conducted in several searchable databases. The keywords used were related to neurodegenerative dementias, ageing and medicinal plants. Boolean operators and filters were used to focus the search. As a result, there is current clinical and preclinical scientific information on 49 species used in traditional medicine for ageing-related problems, including neurodegenerative dementias. There are preclinical and clinical scientific evidences on their properties against protein aggregates in the central nervous system and their effects on neuroinflammation, apoptosis dysregulation, mitochondrial dysfunction, gabaergic, glutamatergic and dopaminergic systems alterations, monoamine oxidase alterations, serotonin depletion and oestrogenic protection. In conclusion, the potential therapeutic effect of the different medicinal plants depends on the type of neurodegenerative dementia and its stage of development, but more clinical and preclinical research is needed to find better, safer and more effective treatments., (© 2023 John Wiley & Sons Ltd.)

The retina may suffer neurodegenerative damages, as other tissues of the central nervous system do, and serious eye diseases may develop. One of them is age-related macular degeneration, which causes progressive loss of vision due to retina degeneration. Treatment of age-related macular degeneration focuses on antioxidant agents and anti-vascular endothelial growth factor compounds, among others, that prevent/diminish oxidative stress and reduce neovascularisation respectively. The phytochemicals, medicinal plants and/or plant-diet supplements might be a useful adjunct in prevention or treatment of age-related macular degeneration owing to their antioxidant and anti-vascular endothelial growth factor properties. This review article presents the most investigated plants and natural products in relation to age-related macular degeneration, such as saffron, ginkgo, bilberry and blueberry, curcuma or turmeric, carotenoids, polyphenols, and vitamins C and E. This study provides up-to-date information on the effects, treatments, safety and efficiency of these phytotherapy products., Competing Interests: None

In vitro viability assays against a representative panel of human cancer cell lines revealed that polyamines L1a and L5a displayed remarkable activity with IC 50 values in the micromolar range. Preliminary research indicated that both compounds promoted G1 cell cycle arrest followed by cellular senescence and apoptosis. The induction of apoptotic cell death involved loss of mitochondrial outer membrane permeability and activation of caspases 3/7. Interestingly, L1a and L5a failed to activate cellular DNA damage response. The high intracellular zinc-chelating capacity of both compounds, deduced from the metal-specific Zinquin assay and Zn L 2+ stability constant values in solution, strongly supports their cytotoxicity. These data along with quantum mechanical studies have enabled to establish a precise structure-activity relationship. Moreover, L1a and L5a showed appropriate drug-likeness by in silico methods. Based on these promising results, L1a and L5a should be considered a new class of zinc-chelating anticancer agents that deserves further development.

Like other tissues of the central nervous system, the retina is susceptible to damage by oxidative processes that result in several neurodegenerative disease such as age-related macular degeneration, diabetic retinopathy, glaucoma, ischaemic retinal disease, retinal disease produced by light oxidation, and detached retina, among other diseases. The use of antioxidant substances is a solution to some health problems caused by oxidative stress, because they regulate redox homeostasis and reduce oxidative stress. This is important for neurodegeneration linked to oxidation processes. In line with this, Ginkgo biloba is a medicinal plant with excellent antioxidant properties whose effects have been demonstrated in several degenerative processes, including retinal diseases associated with neurodegeneration. This review describes the current literature on the role of ginkgo in retinal diseases associated with neurodegeneration. The information leads to the conclusion that G. biloba extracts might be a good option to improve certain neurodegenerative retinal diseases, but more research is needed to determine the safety and efficacy of G. biloba in these retinal degenerative processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

By comparison with close contact interactions between benzene rings there is a paucity of experimental data available for attractive interactions involving aromatic heterocyclic rings, especially for small molecules in solution. Herein we describe aromatic heterocyclic and carbocyclic edge-to face interactions and conformational stereodynamics of N-1,2-diphenylethyl imines bearing a phenyl group and either a 2-pyridyl, 3-pyridyl, 2-thiophene or 2-furanyl moiety on the imino carbon. X-ray crystal structures have been determined for two compounds. Slow rotation about the phenyl-imino bond in the E-isomers and around the heterocycle-imino bond in the Z-isomers of the pyridyl compounds was observed at low temperatures by NMR. Abnormally large shielding of one ortho hydrogen indicates that both the imino phenyl and heterocycle rings can engage in an edge-to-face interaction with the N-terminal phenyl moiety in the appropriate isomer. Some rotational barriers around the phenyl-imino and heterocycle-imino bonds were measured.

A series of compounds containing the sulfonamide scaffold were synthesized and screened for their in vitro anticancer activity against a representative panel of human cancer cell lines, leading to the identification of N-(2-methyl-1H-indol-5-yl)-1-naphthalenesulfonamide (8e) as a compound showing a remarkable activity across the panel, with IC50 values in the nanomolar-to-low micromolar range. Cell cycle distribution analysis revealed that 8e promoted a severe G2/M arrest, which was followed by cellular senescence as indicated by the detection of senescence-associated β-galactosidase (SA-β-gal) in 8e-treated cells. Prolonged 8e treatment also led to the onset of apoptosis, in correlation with the detection of increased Caspase 3/7 activities. Despite increasing γ-H2A.X levels, a well-established readout for DNA double-strand breaks, in vitro DNA binding studies with 8e did not support interaction with DNA. In agreement with this, 8e failed to activate the cellular DNA damage checkpoint. Importantly, tubulin staining showed that 8e promoted a severe disorganization of microtubules and mitotic spindle formation was not detected in 8e-treated cells. Accordingly, 8e inhibited tubulin polymerization in vitro in a dose-dependent manner and was also able to robustly inhibit cancer cell motility. Docking analysis revealed a compatible interaction with the colchicine-binding site of tubulin. Remarkably, these cellular effects were reversible since disruption of treatment resulted in the reorganization of microtubules, cell cycle re-entry and loss of senescent markers. Collectively, our data suggest that this compound may be a promising new anticancer agent capable of both reducing cancer cell growth and motility., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Triazolopyridopyrimidines 3-phenyl-6,8-di(2-pyridyl)-[1,2,3]triazolo[5',1':6,1]pyrido[2,3-d]pyrimidine (1a), 6,8-di(pyridin-2-yl)-[1,2,3]triazolo[1',5':1,6]pyrido[2,3-d]pyrimidine (1b) and 3-methyl-6,8-di(2-pyridyl)-[1,2,3]triazolo[5',1':6,1]pyrido[2,3-d]pyrimidine (1c) were prepared and their electrochemical and luminescence properties were studied in depth. The DNA binding ability of this series of compounds has been investigated by means of UV-vis absorption and fluorescence titrations, steady-state emission quenching with ferrocyanide as well as viscosity measurements. Results have shown that triazolopyridopyrimidine 1a interacts strongly at DNA grooves. This compound also displays preferential binding to GC-rich sequences and the ability to photooxidize guanine. Moreover, these studies have revealed the key role of the phenyl substituent at the triazole ring in the binding affinity of 1a-c. Compounds 1b and 1c did not show appreciable propensity for DNA binding, however these triazolopyridopyrimidines demonstrated to present photoinduced DNA cleavage activity, 1b being more active than 1c. DNA photocleavage mediated by these compounds takes place mainly through single strand scission events and, in a minor extent, through double strand cuts. Mechanistic investigations using radical scavengers showed that both 1b and 1c generate reactive oxygen species (singlet oxygen, superoxide and hydroxyl radicals) upon irradiation. Both type I and type II mechanisms are involved in the photocleavage process. Furthermore, compounds 1a-c were tested for their antiprotozoal activity against four different Leishmania spp. (L. infantum, L. braziliensis, L. guyanensis and L. amazonensis). Triazolopyridopyrimidines 1a and 1c resulted to be more active and selective than the reference drug (miltefosine) in vitro against L. infantum amastigotes. Compound 1a exhibited high leishmanicidal activity against L. infantum spleen forms in the in vivo test.

A new series of triazolopyridyl pyridyl ketones has been synthetized by regioselective lithiation of the corresponding [1,2,3]triazolo[1,5-a]pyridine at 7 position followed by reaction with different electrophiles. The in vitro antileishmanial activity of these compounds was evaluated against Leishmaniainfantum, Leishmaniabraziliensis, Leishmaniaguyanensis and Leishmaniaamazonensis. Compounds 6 and 7 were found to be the most active leishmanicidal agents. Both of them showed activities at micromolar concentration against cultured promastigotes of Leishmania spp. (IC₅₀=99.8-26.8 μM), without cytotoxicity on J774 macrophage cells. These two compounds were also tested in vivo in a murine model of acute infection by L. infantum. The triazolopyridine derivative 6 was effective against both spleen and liver parasites forms, while 7 was inactive against liver parasites. Mechanistic aspects of the antileishmanial activity were investigated by means of DNA binding studies (UV-titration and viscosimetry). Results have revealed that these active ligands are able to interact strongly with DNA [Kb=1.14 × 10(5)M(-1) (6) and 3.26 × 10(5)M(-1) (7)]. Moreover, a DNA groove binding has been proposed for both 6 and 7. To provide more insight on the mode of action of compounds 6 and 7 under biological conditions, their interaction with bovine serum albumin (BSA) was monitored by fluorescence titrations and UV-visible spectroscopy. The quenching constants and binding parameters were determined. Triazolopyridine ketones 6 and 7 have exhibited significant affinity towards BSA [Kb=2.5 × 10(4)M(-1) (6) and 1.9 × 10(4)M(-1) (7)]. Finally, to identify the binding location of compounds 6 and 7 on the BSA, competitive binding experiments were carried out, using warfarin, a characteristic marker for site I, and ibuprofen as one for site II. Results derived from these studies have indicated that both compounds interact at BSA site I and, to a lesser extent, at site II., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We report in vivo and in vitro antileishmanial and trypanocidal activities of a new series of N-substituted benzene and naphthalenesulfonamides 1-15. Compounds 1-15 were screened in vitro against Leishmania infantum , Leishmania braziliensis , Leishmania guyanensis , Leishmania amazonensis , and Trypanosoma cruzi . Sulfonamides 6e, 10b, and 10d displayed remarkable activity and selectivity toward T. cruzi epimastigotes and amastigotes. 6e showed significant trypanocidal activity on parasitemia in a murine model of acute Chagas disease. Moreover, 6e, 8c, 9c, 12c, and 14d displayed interesting IC50 values against Leishmania spp promastigotes as well as L. amazonensis and L. infantum amastigotes. 9c showed excellent in vivo activity (up to 97% inhibition of the parasite growth) in a short-term treatment murine model for acute infection by L. infantum. In addition, the effect of compounds 9c and 14d on tubulin as potential target was assessed by confocal microscopy analysis applied to L. infantum promastigotes.

Our aim was to evaluate the in vitro efficacy of a series of N-benzenesulfonamides of amine substituted aromatic rings, sulfonamides 1-6, against Trypanosoma cruzi and Leishmania spp. and to compare their trypanocidal and leishmanicidal profile. In order to elucidate the probable mechanism of action, the interaction of selected sulfonamides with pUC18 plasmid DNA was investigated by nuclease activity assays. In addition, the cellular targets of these sulfonamides in treated parasites were also searched by transmission and scanning electron microscopy. The most active compounds 4-nitro-N-pyrimidin-2-ylbenzenesulfonamide 1a and 4-chloro-N-5-methyl-thiazol-2-yl-benzenesulfonamide 2d displayed significant in vitro activity against Leishmania spp. promastigotes, without toxicity to J774 macrophages. Selected sulfonamides 1a, 4-nitro-N-pyrazin-2-yl-benzenesulfonamide 1n and 2d were also active against Leishmania infantum intracellular amastigotes. Compounds 1n and 2d showed nuclease activity in the presence of copper salt analogous to our previous results with sulfonamide 1a. Mechanistic data reveal the involvement of a redox process. Evidence for the formation of reactive oxygen species (ROS) responsible for DNA strand scission is provided for sulfonamides 1a, 1n and 2d. Transmission electron microscopic (TEM) analysis of L. infantum promastigotes treated with compounds 1a, 1n and 2d shows an overall cellular disorganization effects which are mainly addressed to DNA bearing structures such as the nucleus, mitochondria and kinetoplast. Disruption of double nuclear membrane and loss of cellular integrity along with accumulation of cytoplasmic electrodense bodies were also frequently observed., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Leishmaniasis, African sleeping sickness and Chagas disease, caused by the kinetoplastid parasites Leishmania spp, Trypanosoma brucei and Trypanosoma cruzi, respectively, are among the most important parasitic diseases, affecting millions of people and considered to be within the most relevant group of neglected tropical diseases. The main alternative to control such parasitosis is chemotherapy. Nevertheless, the current chemotherapeutic treatments are far from being satisfactory. This review outlines the current understanding of different drugs against leishmaniasis, African sleeping sickness and Chagas disease, their mechanism of action and resistance. Recent approaches in the area of anti-leishmanial and trypanocidal therapies are also enumerated, new modulators from the mode of action, development of new formulations of old drugs, therapeutic switching and "in silico" drug design.

A series of compounds containing the nitrobenzene and sulfonamido moieties were synthesized and their leishmanicidal effect was assessed in vitro against Leishmaniainfantum promastigotes. Among the compounds evaluated, the p-nitrobenzenesulfonamides 4Aa and 4Ba, and the p-nitroaniline 5 showed significant activity with a good selectivity index. In a Balb/c mice model of L. Infantum, administration of compounds 4Aa, 4Ba or 5 (5mg/kg/day for 10 days, injected ip route) led to a clear-cut parasite burden reduction (ca. 99%). In an attempt to elucidate their mechanism of action, the DNA interaction of 4Aa and 5 was investigated by means of viscosity studies, thermal denaturation and nuclease activity assay. Both compounds showed nuclease activity in the presence of copper salt. The results suggest that compounds 4Aa, 4Ba and 5 represent possible candidates for drug development in the therapeutic control of leishmaniasis.

A series of 2-sulfonyliminodihydropyrimidine derivatives have been synthesized and evaluated in vivo for their antinociceptive and anti-inflammatory activities. The results were compared with that of acetyl salicylic acid. Compounds 6Ab-d and 6Be displayed an interesting analgesic profile in the acetic acid-induced abdominal contractions test. Based on the results of the carrageenan-hind paw edema test, compound 6Af showed potential anti-inflammatory activity.

To study the utility of the virtual combinatorial chemistry coupled with computational screening, a library of amine and urea derivatives was designed by virtual combinatorial synthesis and eventually computationally screened by a mathematical topological model as antihistaminic compounds. The results reveal that virtual combinatorial synthesis and virtual screening together with molecular topology are a powerful tool in the design of new drugs.

[reaction: see text] N-Carbamoylmethyl-N'-tosyl guanidine 2 reacts easily with primary alkylamines to afford substituted carboxamides 3. The reaction proceeds via a five-membered-ring intermediate 5, which could be isolated, and features a rare example of an intermolecular transamidation reaction under mild conditions.

We have studied the potential anti-inflammatory effects of 20 2-tosylamino and 2-tosyliminopyrimidine new derivatives in human neutrophils. We have evaluated their interference with some leukocyte functions and 5-lipoxygenase activity. All the compounds reduced neutrophil degranulation process at concentrations in the microM range. Besides, compounds with a phenolic substitution inhibited leukotriene B(4) biosynthesis in neutrophils and decreased the cell-free 5-lipoxygenase activity. This study demonstrates that 2-tosylamino and 2-tosyliminopyrimidine derivatives can reduce the activation of neutrophil cells which may have relevance for the modulation of the inflammatory response.