A novel series of formoterolaphthalazinone hybrids were synthesised and evaluated as dual pharmacology I22-adrenoceptor agonists and PDE4 inhibitors. Most of the hybrids displayed high ...I22-adrenoceptor agonist and moderate PDE4 inhibitory activities. The most potent compound, (R,R)-11c, exhibited agonist (EC50 = 1.05 nM, pEC50 = 9.0) and potent PDE4B2 inhibitory activities (IC50 = 0.092 mu M).
Coumarin hybrids have been designed and synthesized as an important new strategy in the field of medicinal chemistry. Coumarin core has been shown to form various compounds to combat several diseases ...including microbial, cancer, inflammatory, and neurodegenerative disorders. Recently, a number of coumarin-based drugs (e.g., coumadin, acenocoumarol, dicoumarol, phenprocoumon, and novobiocin) have been FDA-approved and are in the clinic, and several coumarin-containing compounds are in clinical trials. Our group classified coumarin-based hybrid compounds into groups showing shared biological activities and discussed their potential therapeutic targets.
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Structural hybridization of preclinically and clinically validated pharmacologically active molecules has emerged as a promising tool to develop new generations of safe and highly ...efficient drug candidates against various diseases including microbial infections, virus infections and cancer. Strategies of drug-drug combinations have been adopted to generate hybrid conjugates of many clinically used drugs, designed to address inherent problems associated with these drugs. Thus, the design of hybrids was aimed to achieve higher efficacy through possible multi-target interactions, selective delivery of the drug to the site of action with the aim to improve bioavailability, alleviate toxicity and circumvent drug resistances. In this review article, we summarize the progress made in recent years in the rapidly growing field of drug discovery, focusing on the rationality of the hybrid design with particular emphasis on the linker architecture, which plays a crucial role in the overall success of a hybrid drug.
Heterosis, or hybrid vigor, is exploited by breeders to produce elite high-yielding crop lines, but beneficial phenotypes are lost in subsequent generations owing to genetic segregation. Clonal ...propagation through seeds would enable self-propagation of F
hybrids. Here we report a strategy to enable clonal reproduction of F
rice hybrids through seeds. We fixed the heterozygosity of F
hybrid rice by multiplex CRISPR-Cas9 genome editing of the REC8, PAIR1 and OSD1 meiotic genes to produce clonal diploid gametes and tetraploid seeds. Next, we demonstrated that editing the MATRILINEAL (MTL) gene (involved in fertilization) could induce formation of haploid seeds in hybrid rice. Finally, we combined fixation of heterozygosity and haploid induction by simultaneous editing of all four genes (REC8, PAIR1, OSD1 and MTL) in hybrid rice and obtained plants that could propagate clonally through seeds. Application of our method may enable self-propagation of a broad range of elite F
hybrid crops.
In photocatalysis, the Schottky barrier in metal–semiconductor hybrids is known to promote charge separation, but a core–shell structure always leads to a charge build‐up and eventually shuts off the ...photocurrent. Here, we show that Au–Cu2O hybrid nanostructures can be continuously tuned, particularly when the Cu2O domains are single‐crystalline. This is in contrast to the conventional systems, where the hybrid configuration is mainly determined by the choice of materials. The distal separation of the Au–Cu2O domains in Janus nanostructures leads to enhanced charge separation and a large improvement of the photocurrent. The activity of the Au–Cu2O Janus structures is 5 times higher than that of the core–shell structure, and 10 times higher than that of the neat Cu2O nanocubes. The continuous structural tuning allows to study the structure–property relationship and an optimization of the photocatalytic performance.
The distal arrangement of Au–Cu2O domains in the Janus structure promotes charge separation, leading to a five‐ and tenfold enhancement of the photocurrent of the Au@Cu2O core–shell structure and the neat Cu2O nanocubes, respectively.
Accurate prediction of the phenotypical performance of untested single-cross hybrids allows for a faster genetic progress of the breeding pool at a reduced cost. Yield data of maize hybrids were ...employed to predict the performance of new untested hybrids in late sowing environments. Different groups of predictor hybrids were formed using both data from high and low relatedness between predictors and predicted hybrids and by employing data from low and high yielding environments. A new group of hybrids were formed and evaluated in field trials to validate the predictions. The effectiveness of the predictions was investigated by means of the correlation coefficient between predicted and observed yield values. The best predictions of untested new hybrids were reached by using maximum relatedness information combined with data obtained in the best yielding environments.
•The synthesis of five-five, five-six and six-six antibacterial hybrid heterocycles.•The Docking studies and mechanism of action for synthesized compounds.•The different protocols for the synthesis ...of targeted heterocycles and the mechanisms to account for their formations.
Hybrid molecules have become a well-established and powerful biologically relevant heterocycles. They constitute a core structure due to their widespread use in pharmaceutical and agrochemical industry. In recent years this field has been increasingly grown in an extraordinary manner and is now recognized in fields related to drug discovery. A limitation associated with antibacterial drugs is drug resistance and the harmful side effects, lack of efficiency and the need of prolonged therapy required the use of toxic drugs. An interesting and efficient strategy is the combination of two biologically active scaffolds acting at different targets. It is worth to mention that the nature of substituent's and the ring size play a crucial rule in increasing the potency of such compounds. Accessing such challenge, we focus on recent developments in the synthesis of anti-bacterial hybrid heterocycles, in silico methods, docking studies and mode of action utilizing accessible starting materials, simple and efficient processes as well functional groups diversity.
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