Current scenario of pyrazole hybrids with in vivo therapeutic potential against cancers.

Chemotherapeutics occupy a pivotal role in the medication of different types of cancers, but the prevalence and mortality rates of cancer remain high. The drug resistance and low specificity of current available chemotherapeutics are the main barriers for the effective cancer chemotherapy, evoking an immediate need for the development of novel anticancer agents. Pyrazole is a highly versatile five-membered heterocycle with two adjacent nitrogen atoms and possesses remarkable therapeutic effects and robust pharmacological potency. The pyrazole derivatives especially pyrazole hybrids have demonstrated potent in vitro and in vivo efficacies against cancers through multiple mechanisms, inclusive of apoptosis induction, autophagy regulation, and cell cycle disruption. Moreover, several pyrazole hybrids such as crizotanib (pyrazole-pyridine hybrid), erdafitinib (pyrazole-quinoxaline hybrid) and ruxolitinib (pyrazole-pyrrolo [2,3-d]pyrimidine hybrid) have already been approved for the cancer therapy, revealing that pyrazole hybrids are useful scaffolds to develop novel anticancer agents. The purpose of this review is to summarize the current scenario of pyrazole hybrids with potential in vivo anticancer efficacy along with mechanisms of action, toxicity, and pharmacokinetics, covering papers published in recent 5 years (2018-present), to facilitate further rational exploitation of more effective candidates.

Therapeutic Potential of Indole Derivatives as Anti-HIV Agents: A Mini-review.

Acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), is one of the leading causes of human deaths. The advent of different anti-HIV drugs has turned AIDS/HIV from a deadly infection to chronic and manageable disease. However, the development of multidrug-resistant viruses, along with the severe side effects of anti-HIV agents, has compromised their efficacy and limited the treatment options. Indoles, the most common frameworks in the bioactive molecules, represent attractive scaffolds for designing and developing novel drugs. Indole derivatives are potent inhibitors of HIV enzymes such as reverse transcriptase, integrase, and protease. Furthermore, some indole-based agents, like delavirdine, have already been applied in clinics or are under clinical evaluations for the treatment of AIDS/HIV, revealing that indole moiety is a useful template for the development of anti-HIV agents. This review focuses on the recent advancement in indole derivatives, including indole alkaloids, hybrids, and dimers with anti-HIV potential, covering articles published between 2010 and 2020. The chemical structures, structure-activity relationship, and mechanisms of action are also discussed.

Coumarin-based derivatives with potential anti-HIV activity.

Acquired immunodeficiency syndrome (AIDS), as a result of human immunodeficiency virus (HIV) infection which leads to severe suppression of immune functions, is an enormous world-wide health threat. The anti-HIV agents are critical for the HIV/AIDS therapy, but the generation of viral mutants and the severe side effects of the anti-HIV agents pose serious hurdles in the treatment of HIV infection, and creat an urgent need to develop novel anti-HIV agents. The plant-derived compounds possess structural and mechanistic diversity, and among them, coumarin-based derivatives have the potential to inhibit different stages in the HIV replication cycle, inclusive of virus-host cell attachment, cell membrane fusion, integration, assembly besides the conventional target like inhibition of the reverse transcriptase, protease, and integrase. Moreover, (+)-calanolide A, a coumarin-based natural product, is a potential anti-HIV agent. Thus, coumarin-based derivatives are useful scaffolds for the development of anti-HIV agents. This review article describes the recent progress in the discovery, structural modification, and structure-activity relationship studies of potent anti-HIV coumarin-based derivatives including natural coumarin compounds, synthetic hybrids, dimers, and other synthetic derivatives covering articles published between 2000 and 2020.

Product-oriented decomposition of lignocellulose catalyzed by novel polyoxometalates-ionic liquid mixture.

Lignocellulose was oxidatively decomposed in a newly developed polyoxometalates-imidazolium ionic liquid mixture. Aromatic compounds covering acids, esters, ketones, aldehydes, and phenols were selectively produced under various conditions. 4-Hydroxylbenzoic acid was dominatingly yielded under low temperature and high oxidant concentration. Phenolic compounds were mainly generated at high temperature with a selectivity of 45.1% and a yield of 4.3%, higher than those generated in similar polyoxometalates-ionic liquids system. The products distributions and residues of lignocellulose decomposition under various conditions were characterized; the influences of the ionic liquids anions on the polyoxometalates-ionic liquids complex formation, the acidic and redox properties of the catalyst, and the final products were profoundly investigated; and a tentative reacting process was proposed. The ionic liquid could be recycled for five times. This work not only provided a new lignocellulose decomposition strategy to produce aromatic products, but also offered a guidance for product-oriented lignocellulose decomposition.

Bifunctional and recyclable Dawson-type polyoxometalates catalyze oxidative degradation of lignocellulose to selectively produce phthalates.

Acid-redox bifunctional Dawson-type polyoxometalates K6P2W18O62 (P2W18) and K10P2W17O61 (P2W17) were introduced as the new-type catalysts in oxidative decomposition of lignocellulose. The lignin and hemicellulose ingredients of lignocellulose could be decomposed by P2W17 to produce diisobutyl phthalate with the selectivity of 75.67% and other aromatic and aliphatic compounds under mild conditions, evidently differed from other POMs-catalyzed lignocellulose depolymerization in which aromatic ketones and phenols were the main compounds. Diisobutyl phthalate was obtained from the oxidation of Cα-OR and α-OH of the phenyl structure. The catalyst could be recycled for three times without obvious deactivation. This is the first report of lignocellulose decomposition catalyzed by Dawson-type polyoxometalates to selectively produce phthalates.

Co-immobilization of cellulase and lysozyme on amino-functionalized magnetic nanoparticles: An activity-tunable biocatalyst for extraction of lipids from microalgae.

An activity-tunable biocatalyst for Nannochloropsis sp. cell-walls degradation was prepared by co-immobilization of cellulase and lysozyme on the surface of amino-functionalized magnetic nanoparticles (MNPs) employing glutaraldehyde. The competition between cellulase and lysozyme during immobilization was caused by the limited active sites of the MNPs. The maximum recovery of activities (cellulase: 78.9% and lysozyme: 69.6%) were achieved due to synergistic effects during dual-enzyme co-immobilization. The thermal stability in terms of half-life of the co-immobilized enzymes was three times higher than that in free form and had higher catalytic efficiency for hydrolysis of cell walls. Moreover, the co-immobilized enzymes showed greater thermal stability and wider pH tolerance than free enzymes under harsh conditions. Furthermore, the co-immobilized enzymes retained up to 60% of the residual activity after being recycled 6 times. This study provides a feasible approach for the industrialization of enzyme during cell-walls disruption and lipids extraction from Nannochloropsis sp.