scholarly journals Synthesis of novel aminoquinolines with potential leishmanicidal and antimalarial biological activity / Síntese de novas aminoquinolinas com potencial actividade biológica leishmanicida e antimalárica

2021 ◽  
Vol 7 (12) ◽  
pp. 118095-118105
Author(s):  
Luan Ramalho Pinheiro ◽  
Giovanna Diniz Della Croce ◽  
Francielle Dutra Aguiar ◽  
Bruna de Oliveira Thomasi ◽  
Thaís Mirelli Rêgo Bezerra ◽  
...  

Leishmaniasis is a disease transmitted by different parasite species of the genus Leishmania, while malaria, by protozoa of the genus Plasmodium sp. These diseases affect tropical and subtropical regions, where about half of the world's population live. However, leishmaniasis and malaria are considered neglected diseases because these regions are poor, and consequently have precarious essential sanitation networks. In response to the lack of vaccines and effective medical measures, some natural and synthetic medicines are used as forms of treatment, such as quinoline derivatives necessary to treat malaria. Even so, the parasites have shown resistance to forms of treatment, which makes needed the constant development of new drugs with potential against them. Quinoline derivatives, chloroquine analogues, have potential activity for the diseases of interest, while anilines are molecules used in nucleophilic reactions on different substrates. Therefore, the work consisted of exploring the synthesis between these two compounds through subsequent reactions involving the formation of intermediates that resulted in the products of interest. Twelve novel derivatives with potential leishmanicidal and antimalarial biological activity were synthesized. The molecules produced were purified and rightly characterized by several methods, such as mass spectrometry, infrared spectroscopy, and Nuclear Magnetic Resonance of Carbon (13C) and Hydrogen (1H). Also, were obtained the melting points of the synthesized molecules. Finally, all products were sent for biological tests against the parasites, getting highly effective results for the protozoa responsible for leishmaniasis.

2018 ◽  
Vol 25 (30) ◽  
pp. 3560-3576 ◽  
Author(s):  
Massimo Tosolini ◽  
Paolo Pengo ◽  
Paolo Tecilla

Natural and synthetic anionophores promote the trans-membrane transport of anions such as chloride and bicarbonate. This process may alter cellular homeostasis with possible effects on internal ions concentration and pH levels triggering several and diverse biological effects. In this article, an overview of the recent results on the study of aniontransporters, mainly acting with a carrier-type mechanism, is given with emphasis on the structure/activity relationship and on their biological activity as antibiotic and anticancer agents and in the development of new drugs for treating conditions derived from dysregulation of natural anion channels.


2020 ◽  
Vol 20 (5) ◽  
pp. 396-407 ◽  
Author(s):  
Zhaojun Sheng ◽  
Siyuan Ge ◽  
Min Gao ◽  
Rongchao Jian ◽  
Xiaole Chen ◽  
...  

Embelin is a naturally occurring para-benzoquinone isolated from Embelia ribes (Burm. f.) of the Myrsinaceae family, and contains two carbonyl groups, a methine group and two hydroxyl groups. With embelin as the lead compound, more than one hundred derivatives have been reported. Embelin is well known for its ability to antagonize the X-linked inhibitor of apoptosis protein (XIAP) with an IC50 value of 4.1 μM. The potential of embelin and its derivatives in the treatment of various cancers has been extensively studied. In addition, these compounds display a variety of other biological effects: antimicrobial, antioxidant, analgesic, anti-inflammatory, anxiolytic and antifertility activity. This paper reviews the recent progress in the synthesis and biological activity of embelin and its derivatives. Their cellular mechanisms of action and prospects in the research and development of new drugs are also discussed.


2020 ◽  
Vol 20 (5) ◽  
pp. 342-368 ◽  
Author(s):  
Juliana de Oliveira Carneiro Brum ◽  
Tanos Celmar Costa França ◽  
Steven R. LaPlante ◽  
José Daniel Figueroa Villar

Hydrazones and their derivatives are very important compounds in medicinal chemistry due to their reported biological activity for the treatment of several diseases, like Alzheimer’s, cancer, inflammation, and leishmaniasis. However, most of the investigations on hydrazones available in literature today are directed to the synthesis of these molecules with little discussion available on their biological activities. With the purpose of bringing lights into this issue, we performed a revision of the literature and wrote this review based on some of the most current research reports of hydrazones and derivatives, making it clear that the synthesis of these molecules can lead to new drug prototypes. Our goal is to encourage more studies focused on the synthesis and evaluation of new hydrazones, as a contribution to the development of potential new drugs for the treatment of various diseases.


Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2824 ◽  
Author(s):  
Junhao Jiang ◽  
Hui Zhou ◽  
Qihua Jiang ◽  
Lili Sun ◽  
Ping Deng

As new drugs for the treatment of malignant tumors, transforming growth factor-beta receptor 1 (TGFβR1) antagonists have attracted wide attention. Based on the crystal structure of TGFβR1-BMS22 complex, the pharmacophore model A02 with two hydrogen bond acceptors (HBAs) and four hydrophobic (HYD) properties was constructed. From the common features of active ligands reported in the literature, pharmacophore model B10 was also generated, which has two aromatic ring centers (RAs) and two HYD properties. The two models have high sensitivity and specificity to the training set, and they are highly consistent in spatial structure. Combining the two pharmacophore models, two novel skeleton structures with potential activity were selected by virtual screening from the DruglikeDiverse, MiniMaybridge, and ZINC Drug-Like databases. Four compounds (YXY01–YXY04) with potential anti-TGFβR1 activity were designed based on the new skeleton structures. In combination with Lipinski’s rules; absorption, distribution, metabolism, excretion, and toxicity (ADMET); and, toxicological properties predicted in the study, YXY01-03 with the novel skeleton, good drug-like properties, and potential activity were finally discovered and may have higher safety relative to BMS22, which may be valuable for further research.


ChemInform ◽  
1988 ◽  
Vol 19 (36) ◽  
Author(s):  
E. SURENDER ◽  
B. R. RAO ◽  
B. S. REDDY ◽  
G. V. P. C. MOULI ◽  
Y. D. REDDY

1951 ◽  
Vol 41 (3) ◽  
pp. 577-591 ◽  
Author(s):  
A. B. M. Whitnall ◽  
W. M. McHardy ◽  
G. B. Whitehead ◽  
F. Meerholz

“Gammexane” and DDT, have many advantages over arsenic as tick killing agents. “Gammexane” dips have been used successfully to control the one host arsenic-resistant blue tick, B. decoloratus (Koch) but these dips have not been fully investigated for the control of two- and three-host ticks. The control of the three-host bont tick, A. hebraeum, a vector of “heartwater”, a disease of cattle, sheep and goats, is of great economic importance to South Africa. Larvae and nymphs seem to occur on cattle to a lesser degree than adults, but each stage shows a definite preference for particular sites on the host. For this reason, control measures have to be mainly directed against the adult stage. The effect of “Gammexane”, DDT and arsenical dips, and combinations of these, has been investigated, by making weekly counts of adults on treated and untreated groups of animals. Dipping has been compared with spraying, and the results have been examined in the light of chemical analyses and biological tests with the same samples. The experiments were spread over two consecutive years.Preliminary experiments indicated that all treatments markedly reduced numbers of male bont ticks on the cattle. Weekly arsenical treatments with 0·16 per cent. As2O3 either by dipping or spraying did not reduce the numbers of females, nor did a composite dip-wash of 0·16 per cent. As2O3 and 50 p.p.m. gamma isomer. Dipping in 50 p.p.m. gamma isomer gave slightly better results against females than the above treatments. Encouraging results were obtained by spraying cattle with freshly diluted wash containing 50 p.p.m. gamma isomer, but dipping in 100 p.p.m. also gave satisfactory results. The relative ineffectiveness of dipping as compared with spraying, was found to be due to the loss of biological activity of hexachlorocyclohexane in dipping tanks, where complicating pollution factors appeared.The results of the preliminary experiments were largely confirmed by the second series. Males always outnumbered females in collections where the ticks were removed week by week from cattle. The collections were taken to represent the rate at which cattle became re-infested, and formed a basis on which to gauge the effectiveness of treatments. Males increased in numbers week by week on other untreated control groups of cattle, and eventually greatly outnumbered the females. This suggested that males remained on the hosts longer, and were recorded more than once in the consecutive weekly counts.All treatments reduced the numbers of males. Weekly treatments in 0·16 per cent. As2O3 did not reduce the numbers of females, nor did it prevent them from engorging. Some females laid after removal from cattle so treated but the eggs were sterile, whilst females in a similar state of engorgement, removed from untreated animals, laid fertile eggs. Arsenical treatments should thus eventually control bont ticks.All “Gammexane” treatments appeared more effective than the arsenical treatments. Fresh dilutions of dispersible pastes and powders in the form of sprays gave better results than dipping in the same preparations at comparable concentrations. This was due to a loss in biological activity of the hexachlorocyclohexane as the washes became dirty with use in dipping tanks. This factor makes chemical determinations of dip-washes, based on total hydrolysable chlorine, of little value, unless these data are correlated with some suitable biological test. The addition of 0·03 per cent, copper sulphate in the wash did not prevent the loss of biological activity.Oil emulsion dips, which were known to show a drop in the gamma isomer content with use in dipping tanks, were kept at the desired concentration and biologically active by adding fresh dip each week. In such cases both dip- and spray-washes gave satisfactory results when used at 100 p.p.m. gamma isomer. A combination of 50 p.p.m. gamma isomer and 0·16 per cent. As2O3 used as a dip-wash was not satisfactory in reducing the number of bont ticks, and little better than a fresh spray of 50 p.p.m. gamma isomer alone. The striking results given by a combination of a dispersible powder spray of 50 p.p.m. gamma isomer and 0·1 per cent. p,p′ DDT might be due to persistent action or repellent effect.Arsenic is a stable substance and has been used for many years in dipping tanks to control ticks. It has disadvantages and in the case of the bont tick many females remained attached to the hosts when treated weekly in arsenic, although the engorged females laid sterile eggs. “Gammexane” preparations when used at 100 p.p.m. gave satisfactory results. These preparations, however, lost their biological activity in dipping tanks, and the best results were obtained when they were applied to cattle as fresh sprays.


2021 ◽  
Vol 4 (2) ◽  
pp. 47-53
Author(s):  
N. Y. Monka ◽  
◽  
N. E. Stadnytska ◽  
I. R. Buchkevych ◽  
K. O. Kaplia ◽  
...  

Benzoquinone and its reduced form hydroquinone belong to phenolic compounds and are found in living organisms in free form or in glycosides. They are active substances of some medicinal plants and have a pharmacological effect on the human body. Accordingly, their derivatives are important objects for chemical synthesis and development of new drugs. This article presents the findings of the structural design of substances with benzoquinone or hydroquinone fragment and sulfur-containing compound. By use of appropriate on-line programs a predictive screening of the biological activity and cytotoxicity of thiosulfonate derivatives of benzoquinone and hydroquinone has been conducted. It has been found that they have immense methodological potential to be synthesized by substances with a wide range of biological activities and a high value of probable activity, which substantiates the feasibility of conducting experimental studies on their biological activity, particularly anticancer.


Parasitology ◽  
1997 ◽  
Vol 114 (7) ◽  
pp. 137-144 ◽  
Author(s):  
M. H. ROOS

Parasitic helminths (worms) cause serious infectious diseases in humans and domestic animals. Control of these infections relies mostly on chemotherapeutics (the anthelmintics), but resistance has developed against most of these broad-spectrum drugs in many parasite species. These resistant parasites are being used to elucidate the molecular mechanisms of drug resistance and drug action. This has led to the development of sensitive assays to detect resistant parasites, but this has not delayed the emergence of additional drug resistant parasite populations. Therefore, as development of new drugs by pharmaceutical companies is slow, we may have to be prepared for a time when broad-spectrum drugs are no longer effective, especially against worms of sheep.


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