Antibacterial Potential of Biosynthesized Silver Nanoparticles Using Berberine Extract Against Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa.

The emergence of multidrug resistance in bacterial infections has limited the use of antibiotics. Helping the action of antibiotics is one of the needs of the day. Today, the biosynthesis of nanoparticles (NPs) is considered due to its safety and cost-effectiveness. In this study, we investigated the effect of biosynthesized silver nanoparticles (AgNPs) by Berberine plant extract against standard strains of multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa. Utilized UV-Vis, FTIR, FESEM/EDX, XRD, DLS, and Zeta potential techniques to confirm the biosynthesis of NPs. Then, disk diffusion agar (DDA) and minimum inhibitory concentration (MIC) tests were performed using common classes of standard antibiotics and AgNPs on the mentioned bacteria. The synergistic action between AgNPs and antibiotics was evaluated by the checkerboard method. First, we obtained the confirmation results of the biosynthesis of AgNPs. According to the DDA test, both standard bacterial strains were sensitive to NPs and had an inhibition zone. Also, the MIC values showed that AgNPs inhibit the growth of bacteria at lower concentrations than antibiotics. On the other hand, the results obtained from checkerboard monitoring showed that AgNPs, in combination with conventional antibiotics, have a synergistic effect. The advantage of this study was comparing the antibacterial effect of AgNPs alone and mixed with antibiotics. The antibacterial sensitivity tests indicated that the desired bacterial strains could not grow even in low concentrations of AgNPs. This property can be applied in future programs to solve the drug resistance of microorganisms in bacterial diseases. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01136-y.

8-Geranyloxycarbostyril as a potent 15-LOX-1 inhibitor showed great anti-tumor effects against prostate cancer.

Carbostyrils are quinolone derivatives, with possible growth inhibition properties on cancer cells. Unlike many tumors, 15-Lipoxygenase-1 (15-LOX-1) is highly expressed in prostate cancer (PCa) cells and has oncogenic properties. Here, with the hypothesis that 6-, 7- and 8-geranyloxycarbostyril (GQ) have inhibitory properties on 15-LOX-1, their effects were assessed on PCa cells. Their cytotoxic effects were evaluated by MTT assay and mechanism of cell death was investigated using annexin V/PI staining. Finally, the anti-tumor properties of 8-GQ were assessed in immunocompromised C57BL/6 mice bearing human PCa cells. Accordingly, these compounds could effectively inhibit 15-LOX activity in PCa cells. MTT and flow cytometry tests confirmed their toxic effects on PCa cells, with no significant toxicity on normal cells, and apoptosis was the main mechanism of cell death. In vivo results indicated that use of 8-GQ at 50 mg/kg had stronger anti-tumor effects than 5 mg/kg cisplatin, with fewer side effects on normal tissues. Therefore, 8-GQ can be introduced as a potential drug candidate with 15-LOX-1 inhibitory potency, which can be effective in treatment of prostate cancer, and should be considered for further drug screening investigations.

O-prenylated carbostyrils as a novel class of 15-lipoxygenase inhibitors: Synthesis, characterization, and inhibitory assessment.

Catalyzed peroxidation of unsaturated lipid in animals and plants intimately is linked to the activity of 15-Lipoxygenase enzymes. Lipoxygenases (LOXs) are well known to play an important role in many acute and chronic syndromes such as inflammation, asthma, cancer, and allergy. In this study, a series of mono prenyloxycarbostyrils were synthesized and evaluated as potential inhibitors of soybean 15-Lipoxygenase (SLO) and their inhibitory potencies were compared to mono prenyloxycoumarins which had been reported in the previous works. The synthetic compounds inhibit lipoxygenase enzyme by competitive mechanism like the prenyloxy coumarins. The results showed that position and length of the prenyl moiety play the important role in lipoxygenase inhibitory activity. Among all of the synthetic compounds (coumarin and carbostyril derivatives), 5-farnesyloxycoumarin and 8-farnesyloxycarbostyril demonstrated the best inhibitory activity by IC50  values of 1.1 µM and 0.53 µM, respectively.

Allylphenols as a new class of human 15-lipoxygenase-1 inhibitors.

In this study, a series of mono- and diallylphenol derivative were designed, synthesized, and evaluated as potential human 15-lipoxygenase-1 (15-hLOX-1) inhibitors. Radical scavenging potency of the synthetic allylphenol derivatives was assessed and the results were in accordance with lipoxygenase (LOX) inhibition potency. It was found that the electronic natures of allyl moiety and para substituents play the main role in radical scavenging activity and subsequently LOX inhibition potency of the synthetic inhibitors. Among the synthetic compounds, 2,6-diallyl-4-(hexyloxy)phenol (42) and 2,6-diallyl-4-aminophenol (47) showed the best results for LOX inhibition (IC50 = 0.88 and 0.80 µM, respectively).

Design, synthesis, and SAR study of isopropoxy allylbenzene derivatives as 15-lipoxygenase inhibitors.

OBJECTIVES: Allylbenzenes have been recently developed as inhibitors of lipoxygenases. They decrease peroxidation activity via mimicking 1,4-unsaturated bonds of fatty acids by their allyl portion. We designed and synthesized new derivatives of allyl benzenes (6a-f) with isopropoxy and amide substituents at ortho and meta positions towards allyl group, respectively. The inhibitory potency of the synthetized allylbenzenes against soybean 15-lipoxygenase (SLO) and subsequently structure-activity relationships was assessed. MATERIALS AND METHODS: 3-allyl-4-isopropoxybenzenamine (5) as starting material was synthesized by coupling of 4-nitropheol with allyl bromide, performing Claisen rearrangement and finally reduction of the nitro moiety. Final products 6a-f were prepared via amidation of 5 with the desired acyl chloride. RESULTS: Among the compounds, N-(3-allyl-4-isopropoxyphenyl)adamantan carboxamide (6f) potentially showed best inhibition (IC50 = 1.35 µM) while 6a with cyclopropyl carboxamide moiety was the weakest inhibitor and 6e with phenyl carboxamide moiety showed no effect. Energy minimized 3D structures of the compounds were docked into the active site pocket of SLO. For the aliphatic amides, docking results showed compatibility between inhibitory potency and average Ki of the cluster conformers, in which their allyl moiety oriented towards SLO iron core. For the aliphatic analogs, by enlargement of the amide moiety size the inhibitory potency was increased. CONCLUSION: Docking results showed that orientation of the amide and allyl moieties of the inhibitors in the active site pocket is the major factor in inhibitory potency variation. Based on the mentioned orientation, for cycloaliphatic amides, by enlargement of the amide moiety both inhibition potency and calculated binding energy increases.

Mn-doped ZnS quantum dots-chlorin e6 shows potential as a treatment for chondrosarcoma: an in vitro study.

Chondrosarcoma is the second-most malignant cancer of the bone and routine treatments such as chemotherapy and radiotherapy have not responded to the treatment of this cancer. Due to the resistance of chondrosarcoma to radiotherapy, the combination of therapeutic methods has been considered in recent years. In this study, a novel combination approach is used that allows photodynamic therapy to be activated by X-rays. The synthesis of Mn-doped zinc sulphide (ZnS) quantum dots was carried out and chlorin e6 photosensitiser attached by covalent and non-covalent methods and their application as an intracellular light source for photodynamic activation was investigated. The toxicity of each nanoparticles was evaluated on chondrosarcoma cancer cells (SW1353) before and after radiation. Also, the effect nanoparticle-photosensitiser conjugated type was investigated in the therapeutic efficacy. The characterisation test (SEM, TEM, EDS, TGA, XRD and ICP analyses) was shown successful synthesis of Mn-doped ZnS quantum dots. Chondrosarcoma cancer cell viability was significantly reduced when cells were treated with MPA-capped Mn-doped ZnS quantum dots-chlorin e6 with spermine linker and with covalent attachment (P ≤ 0.001). These results indicate that X-ray can activate the quantum dot complexes for cancer treatment, which can be a novel method for treatment of chondrosarcoma.

A novel class of human 15-LOX-1 inhibitors based on 3-hydroxycoumarin.

Inflammations, sensitivities, and some cancers in mammals are intimately linked to the activity of lipo-oxygenase enzymes. Owing to the importance of these enzymes, mechanistic studies, product analysis, and synthesis of inhibitors have expanded. In this study, a series of hydroxycoumarins, methoxy-3-hydroxy coumarins, and 7-alkoxy-3-hydroxy coumarins were synthesized and evaluated as potential inhibitors of human 15-LOX-1. Among the synthetic coumarins, 7-methoxy-3-hydroxycoumarin derivative demonstrated potent inhibitory activity and the compound, 5f, showed the best result. Radical scavenging assessment, IC50 , HNMR, and DPPH bleaching results indicate that the electronic properties are the major factors for the lipo-oxygenase inhibition potency of the synthetic coumarins. Based on the theoretical studies, it was suggested that the mesomeric effect of the substituent at the seventh position of the benzene ring is one of the major factors in the stability of the oxy-radical intermediate.