Activity

The present study aims to formulate the characterization and distribution of microplastic in the estuarine surface sediments of Kayamkulam estuary, southwest coast of India. The sediments were dominated by fibre and film shaped microplastic substances. The surface sediments were dominated by polyethylene. The distribution of microplastics was significantly higher than that observed in the other study regions, except for Pearl river estuary and Guanabara Bay. The distribution of microplastics was chiefly controlled by estuarine inundating water and the distance of the sampling site from the open sea.During the Covid-19 pandemic, personal protection equipment (PPE) was widely used to control the virus further spared. In this study, the presence of PPE wastes along the coastline of Bushehr port, the Persian Gulf from nine stations was investigated (4 times during 40 days), and their potential for microplastics (MPs) creation was preliminarily assessed. In total, more than 2380 PPE were collected in the study area. No significant differences were found between various beaches regarding their types and common activities. In addition, the estimated disposal rate of PPE per day and year is 350 and 127,750 items, respectively. More than 10% of the collected PPE from Bushehr’s coastal areas on each sampling day were damaged. Based on the microscopic analysis, the left surgical masks and torn plastic gloves in the coastal regions are emerging sources of secondary microfibers and MP particles (mostly fragments and films) in the marine environments, respectively.The development of new molecules for the treatment of leishmaniasis is, a neglected parasitic disease, is urgent as current anti-leishmanial therapeutics are hampered by drug toxicity and resistance. The pyrrolo[1,2-b]isoquinoline core was selected as starting point, and palladium-catalyzed Heck-initiated cascade reactions were developed for the synthesis of a series of C-10 substituted derivatives. Their in vitro leishmanicidal activity against visceral (L. donovani) and cutaneous (L. amazonensis) leishmaniasis was evaluated. The best activity was found, in general, for the 10-arylmethyl substituted pyrroloisoquinolines. In particular, 2ad (IC50 = 3.30 μM, SI > 77.01) and 2bb (IC50 = 3.93 μM, SI > 58.77) were approximately 10-fold more potent and selective than the drug of reference (miltefosine), against L. amazonensis on in vitro promastigote assays, while 2ae was the more active compound in the in vitro amastigote assays (IC50 = 33.59 μM, SI > 8.93). Notably, almost all compounds showed low cytotoxicity, CC50 > 100 μg/mL in J774 cells, highest tested dose. In addition, we have developed the first Perturbation Theory Machine Learning (PTML) algorithm able to predict simultaneously multiple biological activity parameters (IC50, Ki, etc.) vs. any Leishmania species and target protein, with high values of specificity (>98%) and sensitivity (>90%) in both training and validation series. Therefore, this model may be useful to reduce time and assay costs (material and human resources) in the drug discovery process.Artemisinin-based combination therapies (ACTs) have been able to reduce the clinical and pathological malaria cases in endemic areas around the globe. However, recent reports have shown a progressive decline in malaria parasite clearance in South-east Asia after ACT treatment, thus envisaging a need for new artemisinin (ART) derivatives and combinations. To address the emergence of drug resistance to current antimalarials, here we report the synthesis of artemisinin-peptidyl vinyl phosphonate hybrid molecules that show superior efficacy than artemisinin alone against chloroquine-resistant as well as multidrug-resistant Plasmodium falciparum strains with EC50 in pico-molar ranges. Further, the compounds effectively inhibited the survival of ring-stage parasite for laboratory-adapted artemisinin-resistant parasite lines as compared to artemisinin. These hybrid molecules showed complete parasite clearance in vivo using P. berghei mouse malaria model in comparison to artemisinin alone. Studies on the mode of action of hybrid molecules suggested that these artemisinin-peptidyl vinyl phosphonate hybrid molecules possessed dual activities inhibited falcipain-2 (FP-2) activity, a P. falciparum cysteine protease involved in hemoglobin degradation, and also blocked the hemozoin formation in the food-vacuole, a step earlier shown to be blocked by artemisinin. Since these hybrid molecules blocked multiple steps of a pathway and showed synergistic efficacies, we believe that these lead compounds can be developed as effective antimalarials to prevent the spread of resistance to current antimalarials.Hymenialdisine an alkaloid of oroidin class has drawn the attention of researchers owing to its unique structural features and interesting biological properties. Hymenialdisine exhibited promising inhibitory activity against a number of therapeutically important kinases viz., CDKs, GSK-3β etc., and showed anti-cancer, anti-inflammatory, anti-HIV, neuroprotective, anti-fouling, anti-plasmodium properties. Hymenialdisine and other structurally related oroidin alkaloids such as dibromo-hymenialdisine, stevensine, hymenin, axinohydantoin, spongicidines A-D, latonduines and callyspongisines contain pyrrolo[2,3-c] azepin-8-one core in common. Keeping in view of the interesting structural and therapeutic features of HMD, several structural modifications were carried around the fused-azepinone core which resulted in a number of diverse structural motifs like indolo-azepinones, paullones, aza-paullones, darpones and 5,7-dihydro-6H-benzo[b]pyrimido[4,5-d] azepin-6-one. In this review, an attempt is made to collate and review the structures of diverse hymenialdisine and related fused-azepinones of synthetic/natural origin and their biological properties.Harnessing the antioxidant cellular machinery has sparked considerable interest as an efficient anticancer strategy. Activating Nrf2, the master switch of the cellular redox system, suppresses ROS, alleviates oxidative stress, and halts cancer progression. 1,2,4-oxadiazoles are iconic direct Nrf2 activators that disrupt Nrf2 interaction with its endogenous repressor Keap1. This study introduces rationally designed 1,2,4-oxadiazole derivatives that inhibit other Nrf2 suppressors (TrxR1, IKKα, and NF-kB) thus enhancing Nrf2 activation for preventing oxidative stress and carcinogenesis. Preliminary screening showed that the phenolic oxadiazoles 11, 15, and 19 were comparable to ascorbic acid (ROS scavenging) and EDTA (iron chelation), and superior to doxorubicin against HepG-2, MDA-MB231, and Caco-2 cells. They suppressed ROS by 3 folds and activated Nrf2 by 2 folds in HepG-2 cells. Mechanistically, they inhibited TrxR1 (IC50; 13.19, 17.89, and 9.21 nM) and IKKα (IC50; 11.0, 15.94, and 19.58 nM), and downregulated NF-κB (7.6, 1.4 and 1.9 folds in HepG-2), respectively. They inhibited NADPH oxidase (IC50; 16.4, 21.94, and 10.71 nM, respectively) that potentiates their antioxidant activities. Docking studies predicted their important structural features. Finally, they recorded drug-like in silico physicochemical properties, ADMET, and ligand efficiency metrics.1H Nuclear Magnetic Resonance relaxometry has been applied to reveal dynamical properties of water molecules embedded into egg yolk and white of three species turkey, chicken and quail. Two fractions of water molecules, referred to as confined-water and free-water fractions, have been revealed. CC-885 in vitro It has been demonstrated that translation diffusion of the confined-water fraction is three-dimensional. The dynamics of the confined-water has been quantitatively described in terms of diffusion coefficients and rotational correlation times. The parameters have been compared for egg yolk and white for all the species. In addition to these quantities, the number of the confined-water molecules per unit volume has been provided for all cases. The obtained parameters provide insight into the dynamics of water in eggs of different origin and allow to identify similarities and differences between them in connection to the structure of the network formed by the macromolecular fraction of egg yolk and white.As bisphenol A (BPA) is an extensively used chemical for manufacturing plastic products, discharge of BPA into the environment has caused serious threats to ecology. Therefore, -based chemical oxidation methods have been employed for eliminating BPA. Because monopersulfate (MNP) has become a popular reagent for obtaining , and Co is the most efficient metal for activating MNP, it is critical to develop heterogeneous Co catalysts for easier implementation and recovery. Herein, a unique Co-based catalyst is proposed by utilizing tubular-structured N-doped carbon substrates, derived dicyandiamide (DCDA), to confine Co nanoparticles (NPs). Through simple pyrolysis of a mixture of Co/DCDA, DCDA would be transformed into N-doped carbon nanotubes (CNT) to wrap the resultant Co NP, and, interestingly, this N-doped CNT would exhibit a special bamboo-like morphology. More importantly, as Co NPs are mono-dispersed and singly-confined in N-doped CNTs, forming CoCNT, CoCNT exhibits significantly higher catalytic activities than Co3O4, for activating MNP to degrade BPA. The enhancement of catalytic activities in CoCNT would be possibly ascribed to the synergistic effects between Co NP and the N-doped CNT which not only acts as the support/protection but also provides active sites. Therefore, CoCNT + MNP could lead to a much lower Ea (i.e., 13.8 kJ/mol) of BPA degradation than the reported Ea values. Besides, CoCNT is still effective for eliminating BPA even in the presence of high-concentration NaCl and surfactants. CoCNT is also reusable over many cycles and retains its catalytic activity with 100% BPA removal, demonstrating that CoCNT is an advantageous and robust catalyst for MNP activation.A first test of the field capabilities of a novel in situ sampling technique combining active and passive sampling (APS) was conducted in the sea. The proof-of-concept device uses a pump to draw water into a diffusion cell where dissolved target substances are accumulated onto sorbents which are selective for different classes of contaminants (i.e., metal cations, polar and non-polar organic compounds), simultaneously. A controlled laminar flow established in the diffusion cell enables measurements of contaminant concentrations that are fully independent from the hydrodynamic conditions in the bulk solution. APS measurements were consistent with those obtained using conventional passive sampling techniques such as organic diffusive gradients in thin films (o-DGT) and silicone rubber (SR) samplers (generally less then 40% difference), taking into account the prevailing hydrodynamic conditions. The use of performance reference compounds (PRC) for hydrophobic contaminants provided additional information. Field measurements of metal ions in seawater showed large variability due to issues related to the device configuration. An improved field set-up deployed in supplementary freshwater mesocosm experiments provided metal speciation data that was consistent with passive sampling measurements (DGT), taking into account the hydrodynamic conditions. Overall, the results indicate that the APS technique provides a promising approach for the determination of a wide range of contaminants simultaneously, and independently from the hydrodynamic conditions in the bulk solution.