Here we show the novel anti-helminthic potential of Lansium parasiticum aqueous extract-protected silver nanoparticles (LAgNPs) against albendazole-resistant gastrointestinal parasite Haemonchus contortus. LAgNPs showed LD50 values of 65.6 ± 32.8 nM (12 h), 139.6 ± 39.9 nM (12 h), and 64.3 ± 8.5 nM (24 h) against adult male, female, and L3 larvae, respectively. LAgNPs was also quite effective in inhibiting egg hatching, with an IC50 value of 144.4 ± 3.1 nM at 48 h of exposure. Exposure to LAgNPs generated oxidative stress and mediated physical damage in the worms' tissue. A sharp increase in reactive oxygen species and nitric oxide synthase levels was prominent due to LAgNPs' exposure. In response to oxidative stress, a sharp increase of stress-responsive enzymes' activity, like catalase, superoxide dismutase, and glutathione peroxidase activity, along with the concentration of glutathione, was observed in worm tissue, which indicated a LAgNP-responsive alteration of metabolism. The results give rise to the opportunity for the development of alternative treatment for drug-resistant parasitic worms.
The Michael addition of amines with enones for synthesizing β‐amino carbonyls constitutes a valuable transformation in organic chemistry. While various catalyst have been made available for catalyzing the Michael addition of aromatic amines to enones but there is no report of using α‐amylase enzyme to catalyze this transformation. The α‐amylase from Aspergillus oryzae was found to catalyze the Michael addition of various aryl (hetero) amines to methyl vinyl ketone with high catalytic efficiency (63–83% yield). A hybrid of α‐amylase with copper nanoparticle (α‐amylase@CuNPs) has been prepared and used to catalyze this transformation as a reusable catalyst. Further, an application of α‐amylase catalyzed aza‐Michael addition in the cascade reactions has been exhibited by synthesizing biologically important 3‐acetyl quinoline. In addition, molecular docking and molecular dynamics (MD) simulation studies are carried out to get insight into the key interactions of the substrates with the amino acid residues near the active site and the probable reaction mechanism, which reveals Glu230 and Asn295 play a crucial role in the substrate activation process.
Prevalence of infection, limited choice of drugs, and emerging resistance against contemporary drugs lead to a pressing need to develop new anthelmintic drugs and drug targets. However, limited understanding of the physiology of worms has delayed the process substantially. Here, for the first time, we are reporting the tissue morphology of Haemonchus contortus and targeting its nervous system with quercetin, a naturally occurring flavonoid. Quercetin showed anthelmintic activity against all of the developmental stages of the H. contortus. Further, histological analysis demonstrated damage of various body parts, including isthmus, brut, pseudocoele, and other organs due to quercetin treatment. Mechanistic studies revealed the generation of oxidative stress and alterations in activities of the stress response enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase. Moreover, the time-dependent imaging of ROS-generation disclosed neuropils as the primary targets of quercetin in the adult worms, which eventually lead to the paralysis and death of the worms. Thus, altogether, this work demonstrates that the nervous system of the parasitic helminth, H. contortus, is a novel target of the drug quercetin.
High Prevalence of infection rate, limited choice of drugs, and emerging resistance against these leads to a pressing need for the development of new antihelminthic drugs and drug targets. However, limited understanding of the physiology of worms has delayed the process substantially. Here, for the first time, we are reporting the tissue morphology of Haemonchus contortus, and target its nervous system with quercetin, a naturally occurring flavonoid. Quercetin showed anthelmintic activity against all developmental stages of the nematode. Histological analysis demonstrated damage of various body parts including isthmus, brut, pseudocoele, and other organs. Mechanistic studies revealed the generation of oxidative stress and alteration of the stress response enzyme activities. Importantly, the time-dependent imaging of ROS generation revealed the neuronal system as the primary target of quercetin in adult worms, which eventually leads to the paralysis and death of the worms. This work demonstrates the neuronal system as a novel drug target for quercetin.
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