Hybrid Compounds as Direct Multitarget Ligands: A Review de Oliveira Pedrosa, Michelle; Duarte da Cruz, Rayssa Marques; de Oliveira Viana, Jessika ...
Current topics in medicinal chemistry,
04/2017, Volume:
17, Issue:
9
Journal Article
Peer reviewed
Molecular Hybridization is an approach in rational drug design where new chemical entities are obtained by combining two or more pharmacophoric units from different bioactive compounds into a single ...molecule. Through this approach, medicinal chemists hope that the new hybrid derivative presents: better affinity and efficacy when compared to the parent drugs; a modified selectivity profile with improvement over pharmacokinetic and pharmacodynamic restrictions; dual or multiple modes of action; reduction of undesirable side effects; decreases in drug-drug interactions; reduced emergence or spread of drug resistance in microorganisms and protozoans; and lower cost. The approach has been successfully used by many research groups around the world and has had very promising results with diseases having multifactorial profiles, like Alzheimer´s, Parkinson´s disease, cancer, inflammation, and hypertension among others. The purpose of this paper is to conduct an updated review of molecular hybridization and multitarget profiling (a rational drug design approach), and its applications to the design and discovery of novel hybrid compounds with anti-inflammatory, antimicrobial, anticancer and antiprotozoal (leishmaniasis, malaria, and schistosomiasis) activities over the last six years.
The use of natural products for the treatment of disease is one of the oldest cultures exists. Currently, the research of new drugs using natural products shows a poorly explored biodiversity and a ...great interest of marketing. The enzymatic inhibition by some natural products is investigated among these is the inhibition of hyaluronidase and the consequent reduction of the degradation of hyaluronic acid. So there is a reduction of inflammation and angiogenesis. This study reports the main natural species studied in inhibiting human hyaluronidase that can be the subject of future research for new drugs.
The synthetic hormone sodium levothyroxine (LTX) is one of the most prescribed drugs in the world and the most effective in hypothyroidism treatment. The presence of LTX in the environment has become ...a matter of major concern due to the widespread use of this hormone and by the fact that it is only partially removed in conventional water and sewage treatment plants. However, information regarding the photochemical fate of this hormone in environmental or engineered systems is scarce in the literature. In this work, the sunlight-driven direct and indirect LTX degradation was investigated by determining the photolysis quantum yield,
Φ
LTX
= 3.80 (± 0.02) × 10
−5
, as well as the second-order kinetic constants of the reactions with hydroxyl radicals,
k
LTX,•OH
= 1.50 (± 0.01) × 10
10
L mol
−1
s
−1
and singlet oxygen,
k
LTX,1O2
= 1.47 (± 0.66) × 10
8
L mol
−1
s
−1
. Mathematical simulations indicate that LTX photodegradation is favored in shallow, nitrite-rich, and dissolved organic matter (DOM)-poor environments, with LTX half-life times varying from less than 10 days to about 80 days. LTX removals of 85 and 95% were achieved by UVC photolysis and UVC/H
2
O
2
after 120 min, respectively. Three transformation products, triiodothyronine, diiodothyronine, and diiodotyrosine, were identified during LTX degradation by the UVC-based processes studied. The results herein regarding photo-induced kinetics coupled with environmental fate simulations may help evaluate LTX persistence and also the design of water and wastewater treatment processes.
The photocatalytic degradation of imazethapyr, a herbicide of the imidazolinone family, was investigated in an aqueous suspension of titanium dioxide used as a catalyst. A pseudo-first order kinetic ...model was employed to discuss the results. The effect of catalyst loading, initial concentration of imazethapyr, hydrogen peroxide, pH value, and temperature were investigated. Imazethapyr disappearance as a function of irradiation time was analyzed by HPLC. The ammonium ion formation was determined spectrophotometrically at 694 nm. The degradation was observed to proceed more favorably at natural pH (ca. 4.4) when the pH was varied in the range from 2 to 11. The addition of hydrogen peroxide to the TiO2 suspension enhanced the degradation rate constant up to 5.0x10(-3) mol l-1, but decreased it at higher concentrations. The degradation rate constants decreased by 19% with a temperature increase from 20 to 40 degrees C in the TiO2 suspension, whereas a 16% increase in imazethapyr direct photolysis was observed for the same temperature range. This behavior indicates the occurrence of physisorption between TiO2 and imazethapyr molecules.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Quantitative structure–activity relationship (QSAR) models were proposed to correlate structural features or property descriptors of compounds with their corresponding biological activities. Because ...of the huge number of descriptors that encode different structural features used to generate valid QSAR models, variable selection becomes a fundamental step in building predictive and interpretative models. In this study, we applied a combined approach using multiple linear regression (MLR) and partial least-squares regression (PLS) to generate robust QSAR models with only a few descriptors applied to a set of cruzain inhibitors, namely, 61 semicarbazones and analogues, taken from the literature. From the 4885 descriptors generated by the Dragon program, we selected only five descriptors, applying the “Best-First” algorithm and PLS, followed by analysis of frequency and, finally, the genetic algorithm with MLR. The most significant QSAR equation encodes important steric and electronic structural features, which helps to identify in the set, structures that increase or decrease the pIC50 values measured against cruzain.
•Combined approach using MLR and PLS to generate robust QSAR models•A set of 61 cruzain inhibitors and 4885 DRAGON descriptors were used.•Selected only 5 descriptors and identified structures that are related to activity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
6.
BRASIL FRENTE À ESCASSEZ DE ÁGUA de Menezes Olivo, Andréia; Mitsugu Ishiki, Hamilton
Colloquium humanarum,
12/2014, Volume:
11, Issue:
3
Journal Article
Peer reviewed
Open access
The water is a vital resource to human and this shortage was resulted by rapid and unplanned population growth that contributes to reduce its offer, especially due to the water pollution caused by ...the human. Thinking about it , this revision have with objective discusses the water environmental value, the causes and consequences of its scarcity, as well as the problems that affect the water quality and consequently the man life. It also aims to expose the impacts of their scarcity and what might be the consequences of anthropogenic action and disregard for water. For this, was performad a research bibliographic descriptive and analytical in the current situation this resource in Brasil and the world, guided in books, scientific articles and documentaries, seeking to demonstrate the importance of water to the ecosystem, the problematic and the impacts of it scarcity for society.
Gastrointestinal stromal tumors (GISTs) are unusual cancers, which are developed in specialized cells in the gastrointestinal tract wall. Various strategies involving single-agents, combinations, and ...rapid complementary inhibitor cycling are now being used to control such tumors. Based on promising early clinical trial experience, certain novel KIT and PDGFRA tyrosine kinase inhibitors have shown advanced clinical development. Resistance to tyrosine kinase inhibitors has brought immense difficulties, with patients now requiring additional therapeutic options. This review describes and discusses the last five years (2016-2020) in developing novel c-KIT kinase inhibitors using virtual screening and docking approaches. Computational techniques can be used to complement experimental studies to identify new candidate molecules for therapeutic use. Molecular modeling strategies allow the analysis of the required characteristics that compounds must have to effectively bind c-KIT. Through such analyses, it is possible to both discover and design novel inhibitors against cancer-related proteins that play a critical role in tumor development (including mutant strains). Docking showed potential in the detection of the key residues responsible for ligand recognition and is very helpful to understand the interactions in the active site that can be used to develop new compounds/classes of anticancer drugs and help millions of cancer patients.
BRASIL FRENTE À ESCASSEZ DE ÁGUA Andréia de Menezes Olivo; Hamilton Mitsugu Ishiki
Colloquium humanarum,
05/2015, Volume:
11, Issue:
3
Journal Article
Peer reviewed
Open access
A água é uma fonte vital para o ser humano e sua escassez resulta do crescimento populacional rápido e desordenado, e acaba contribuindo para a redução da sua oferta, especialmente devido à poluição ...dos mananciais causadas pelo próprio homem. Pensando nisto, esta revisão tem como objetivo abordar o valor ambiental da água, às causas e consequências da sua escassez, bem como dos problemas que afetam a qualidade da água e por consequência a vida do homem. Pretende ainda expor os impactos de sua escassez e quais podem ser os reflexos da ação antropogênica e o descaso para com este bem. Para isto, foi realizada uma pesquisa bibliográfica descritiva e analítica da atual situação deste recurso no Brasil e no mundo, pautada em livros, artigos científicos e documentários, visando demonstrar a importância da água para o ecossistema, à problemática e os impactos de sua escassez para a sociedade.
BRASIL FRENTE À ESCASSEZ DE ÁGUA Andréia de Menezes Olivo; Hamilton Mitsugu Ishiki
Colloquium humanarum,
05/2015, Volume:
11, Issue:
3
Journal Article
Peer reviewed
Open access
A água é uma fonte vital para o ser humano e sua escassez resulta do crescimento populacional rápido e desordenado, e acaba contribuindo para a redução da sua oferta, especialmente devido à poluição ...dos mananciais causadas pelo próprio homem. Pensando nisto, esta revisão tem como objetivo abordar o valor ambiental da água, às causas e consequências da sua escassez, bem como dos problemas que afetam a qualidade da água e por consequência a vida do homem. Pretende ainda expor os impactos de sua escassez e quais podem ser os reflexos da ação antropogênica e o descaso para com este bem. Para isto, foi realizada uma pesquisa bibliográfica descritiva e analítica da atual situação deste recurso no Brasil e no mundo, pautada em livros, artigos científicos e documentários, visando demonstrar a importância da água para o ecossistema, à problemática e os impactos de sua escassez para a sociedade.
O crescimento industrial mundial está cada vez mais interligado com os diversos meios sustentáveis, a fim de diminuir os problemas ambientais causados pelo crescimento desenfreado ocorrido até o ...momento, um meio alternativo encontrado foi a substituição parcial do agregado miúdo pelo polímero elastomérico. O concreto piloto apresentou uma resistência de 20,5 MPa após o término do período de cura aos 28 dias de idade, já nos concretos confeccionados com a adição do polímero, observou-se uma perda de resistência. Verificou-se também a queda da massa específica, aumento do índice de vazios e absorção de água conforme se adicionava o polímero. Com os resultados então coletados pode-se indicar as possíveis áreas de atuação, tais com: guias, sarjetas e mobiliários urbanos.
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