A green one-pot synthetic protocol of hexahydropyrimido[4,5-d]pyrimidin-4(1H)-one derivatives: molecular docking, ADMET, anticancer and antimicrobial studies.

Ten hexahydropyrimido[4,5-d]pyrimidine derivatives have been synthesized by using a green and time-efficient microwave method. The synthesized motifs were evaluated for their anticancer activity, antimicrobial activity, molecular docking, drug likeliness and ADMET studies. Comparatively, the hetero-aromatic pyrazole substituted compound 4a exhibited the highest anticancer activity [Mean growth percent: 35.57], while EDG [-N(CH3)2] substituted compound 4i indicated very good activity [Mean growth percent: 60.92] against various cell lines. From the computational studies, Compound 4a passed the drug-likeness and ADME properties, fewer toxic properties, and potent inhibitory potential against the RIPK2 with significant binding affinity. In-silico molecular docking revealed that the compound 4a has significant binding energy (- 9.8 kcal/mol) and dissociation constant (0.54 µM) properties. Additionally, synthesized motifs were evaluated for antimicrobial activity by MIC referencing the standards. According to the SAR evaluations, the compounds 4f (4-NO2), 4g (3-NO2), and 4h (2-Cl) that include EWGs substituted aldehydes performed well as antimicrobials against selected bacterial and fungal strains. Thus, the synthesized pyrimido[4,5-d]pyrimidine with the heterocyclic and EWGs substituents could act as a potential candidate after further structural optimization for anticancer and antimicrobial drug discovery, respectively.

Leveraging new approach methodologies: ecotoxicological modelling of endocrine disrupting chemicals to Danio rerio through machine learning and toxicity studies.

New approach methodologies (NAMs) offer information tailored to the intended application while reducing the use of animals. NAMs aim to develop quantitative structure-activity relationship (QSAR) and quantitive-Read-Across structure-activity relationship (q-RASAR) models to predict and categorize the acute toxicity of known and unknown endocrine-disrupting chemicals (EDCs) against zebrafish. EDCs are a diverse group of toxic substances that disrupt the endocrine system of humans and animals. The q-RASAR model was constructed and verified using validation metrics (R2 = 0.886 and Q2 = 0.814) which found to be more reliable model compare to QSAR model. The substructure fingerprint was well-fitted for the classification model and it was validated using 10-fold average accuracy (Q = 86.88%), specificity (Sp = 88.89%), Matthew's correlation curve (MCC = 0.621) and receiver operating characteristics (ROC = 0.828). The dataset of unknown substances revealed that phenolphthalein (Php) exhibited a significant level of toxicity based on q-RASAR model. The docking and simulation study indicated that the computationally derived important features successfully bound to the target zebrafish sex hormone binding globulin (zfSHBG). The experimental LC50 value of 0.790 mg L-1 was very close to the predicted value of 0.763 mg L-1, which provides high confidence to the developed model.

Role of emerging chitosan and zeolite-modified adsorbents in the removal of nitrate and phosphate from an aqueous medium: A comprehensive perspective.

Due to industrialization and population growth, freshwater supplies are diminishing and becoming impure with high organic pollutant concentrations such as nitrate and phosphate, which shows a high adverse impact on aquatic and human lives. In drinking water sources, particularly groundwater, nitrate is considered as one of the major pollutants which causes methemoglobinemia (in newborn infants), carcinogenic activities and diabetes. Excess concentration of phosphate leads to eutrophication and death of aquatic species due to reduced dissolved oxygen content. Therefore, all countries must implement highly effective technologies for treating wastewater. Chitosan and zeolite are naturally occurring and cost-effective adsorbent materials with a higher surface area that exhibit greater nitrate and phosphate adsorption. Surface modification of chitosan and zeolite increases the adsorption capacity of adsorbents for the removal of both anions selectively. This paper reviews the current development of modified chitosan and zeolite adsorbents for anion adsorption, with an emphasis on modification by zero and multivalent metals and metal oxides, different surfactants, biomass-derived carbon, and natural and synthetic polymers. Multiple adsorption parameters, optimum adsorption condition, adsorption mechanism, regeneration study, research gap and future aspects have been explained for further research work.