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Abstract Thirty-six N -arylsulfonyl-3-substituted indoles were designed and synthesized by combining the N -arylsulfonylindoles with aminoguanidine, semicarbazide, and thiosemicarbazide, respectively. Their antibacterial activities were screened, and cytotoxic activities were evaluated. The results showed that aminoguanidines (6) exhibited much better antibacterial activity than semicarbazides (7) and thiosemicarbazides (8). Most compounds in series 6 showed potent inhibitory activity against the tested bacterial strains, including multidrug-resistant strains, with MIC values in the range of 1.08–23.46 μM. The cytotoxic activity of the compounds 6c , 6d , 6h , 6j , 6k and 6l was assessed in two human cancer cell lines A590 and SGC7901, and one human normal cell line HEK 293T. The results indicated that compounds selected exhibited excellent activity against the tested cancer cells with IC 50 values in the range of 1.51–15.12 μM suggesting the potential of them as new antibacterial and anticancer agents. What's more, the results of resistance study revealed that resistance of the tested bacteria toward 6d is not easily developed. Molecular docking studies revealed that the aminoguanidine and arylsulfonylindole moieties played a significant role in binding the target site of E. coli FabH-CoA receptor. Graphical abstract Image 1 Highlights • N-arylsulfonylindoles containing an aminoguanidine showed excellent inhibitory activity against multidrug-resistant strains. • Anti-cancer activity was also confirmed with a high selectivity. • Resistance of strains S. aureus and E. coli toward 6d is not easily developed. • Molecular docking studies suggested the FabH was involved in the antibacterial activity of 6d. [ABSTRACT FROM AUTHOR]

In this paper, cadmium (Cd) stress tests were performed on Eisenia fetida in sterile artificial soil, and its regulatory mechanism between microbial communities in vivo and in vitro after Cd stress was explored. In the test, 0, 50, 100, 125, 250 and 500 mg kg−1 Cd stress concentrations were implemented. After long-term and short-term stress, the microbes in the earthworms and the soil were cultured with ECO plates. The data statistics of carbon source utilization intensity were carried out using the method developed by our team. CCA was scientifically integrated into TOPSIS to establish a new data analysis model to find the regulatory nodes after stress (Ning et al., 2020). Macro gene sequencing technology revealed that the species with the highest absolute abundance in the microbial communities in vivo and in vitro were all unnamed new species. It was confirmed that the HBA gene, NEUROD1 gene and ABCA3 gene were the regulatory genes of the microbial community in the earthworms under Cd stress, while the TC.FEV.OM gene and cheBR gene were the main regulatory genes of the microbial community in the soil. These results provide a scientific and theoretical reference and model basis for the bioremediation of Cd-contaminated soil and the detoxification mechanism of earthworms. [Display omitted] • The regulatory process of the microbes in worm and in soil is revealed. • CCA and TOPSIS are combined to study the regulatory mechanism of earthworm. • Cd-tolerant microbes are a new unnamed species in the Massilia genus. • HBA, NEUROD1 and ABCA3 are the regulatory genes of the microbes in worm. • TC.FEV.OM and cheBR are the regulatory genes of the microbes in soil. [ABSTRACT FROM AUTHOR]

Earthworms, as the first choice for soil monitoring and bio-remediation of cadmium (Cd)-contaminated soil, need to identify its mechanism under Cd stress. In this study, an artificial soil test method was used to determine the oxidative stress reaction indices, amino acid composition, and microbial community changes in earthworms under different stress durations and concentrations. For the first time, the canonical correlation analysis model and path analysis model were innovatively introduced into the data analysis to determine the mechanism that drives earthworm physiological functions after Cd stress. The results showed that in the low-stress concentration treatments (50–125 mg.kg−1 DW), there was a driving relationship between oxidative stress reaction and microbial community in earthworm, and the driving factor was glycyl-L-glutamic acid at 50 mg.kg−1 DW. With the increase of Cd stress intensity, the enzymes of oxidative stress promoted the survival microbes to begin to proliferate, and SOD became the main driving factor under 125 mg.kg−1 DW Cd stress. In the high-stress concentration treatments (250–500 mg.kg−1 DW), the driving effects were weakened or disappeared; while Cd-resistant microbial population appeared. This study provides a theoretical basis for the driving mechanism between oxidative stress effect and microbial community after Cd stress. Unlabelled Image • CCA and PA are combined to study the toxicological mechanism of earthworm. • The driving process of the physiological function of earthworm is revealed. • At 50 mg kg−1 DW, the microbes can use glycyl-L-glutamic acid start driving effect. • At 125 mg.kg−1 DW, SOD is the main driving factor. • At 250–500 mg.kg−1 DW, driving effects are weakened, and Cd-resistant microbes appeared. [ABSTRACT FROM AUTHOR]

In this study, a series of 1,3,4-oxadiazole derivatives (5a-s , 10a-s , and 16a-d) were designed and synthesized using maximal electroshock (MES) and subcutaneous pentylenetetrazole (sc PTZ) models, to test the anticonvulsant activity of the target compounds in vivo. The neurotoxicity (NT) of the target compounds was measured using the rotating rod (ROT) method. Seven compounds with potential activity were selected to test the 50% effective dose (ED 50) and 50% toxic dose (TD 50). Pharmacological experiments revealed that 6-((5-(pentylthio)-1,3,4-oxadiazol-2-yl)methoxy)-3,4-dihydroquinolin-2(1 H)-one (5b) showed the best anticonvulsant activity (MES, ED 50 = 8.9 mg/kg; sc PTZ, ED 50 = 10.2 mg/kg), which was greater than the activities of carbamazepine and ethosuximide. Compound 5b exhibited the most potent binding affinity toward the GABA A receptor (IC 50 = 0.11 μM) in the in vitro binding experiments. Compound 5b displayed significant anxiolytic activity at a low dose (1 mg/kg) in the elevated plus maze (EPM) test. The GABA content in rat brains was also investigated, and the results showed that compound 5b might have affected the GABA system. In our molecular docking experiment, compound 5b showed significant interactions with residues present at the benzodiazepine binding site on the GABA A receptor. The structure and physicochemical and pharmacokinetic properties of the target compound were predicted using Discovery Studio 2019 and ChemBioDraw Ultra 14.0. Finally we demonstrated that compound 5b mainly acted on GABA A receptor. Thus the present study has provided potential candidates for further investigation in epilepsy. Image 1 • Three different series of new 1,3,4-oxadiazole derivatives were synthesized. • The target compounds were studied in vivo and vitro. • Compound 5b showed the best anticonvulsant activity. • In silico studies were carried out to explore the binding interaction of the most active compound. [ABSTRACT FROM AUTHOR]

Abstract Naphthalimide platinum(IV) antitumor complexes with potential dual DNA damage mechanism were designed, synthesized and evaluated for antitumor activities. The incorporation of DNA targeted naphthalimide group to the platinum(IV) system exerts much positive impacts on their antitumor efficacy. The mechanism research reveals that the title compounds could interact with dsDNA in platinum(IV) form via the naphthalimide group and cause DNA lesion. The further reduction would release platinum(II) complexes and naphthalimide acids which would induce remarkable secondary damage to DNA. Furthermore, the naphthalimide platinum(IV) compounds could combine with human serum albumin via electrostatic force, which are favourable for their storage and transport in blood. Moreover, the title compounds exhibit higher accumulation in tumor cells, and exert lower toxic and higher safe properties than oxaliplatin in vivo. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]