First In Vitro-In Silico Analysis for the Determination of Antimicrobial and Antioxidant Properties of 2-(4-Methoxyphenylamino)-2-oxoethyl Methacrylate and p-Acetamide.

The antibacterial, antifungal, and antioxidant activities of 2-chloro-N-(4-methoxyphenyl)acetamide (p-acetamide) and 2-(4-methoxyphenylamino)-2-oxoethyl methacrylate (MPAEMA) were investigated by in vitro experiments and in silico analyses. MPAEMA has an antibacterial effect only against Gram-positive Staphylococcus aureus. It was determined that this did not affect any other bacteria and Candida glabrata yeast. On the other hand, p-acetamide showed antimicrobial activity against S. aureus ATCC 25923, C. glabrata ATCC 90030, Bacillus subtilis NRRL 744, Enterococcus faecalis ATCC 551289, Escherichia coli ATCC 25922, Klebsiella pneumoniae NRLLB4420, Pseudomonas aeruginosa ATCC 27853, and Listeria monocytogenes ATCC 1911. p-Acetamide showed the greatest antifungal effect by inhibiting the colony growth of Trichoderma longibrachiatum (98%). This was followed by Mucor plumbeus with 83% and Fusarium solani with 21%. MPAEMA inhibited colony growth of T. longibrachiatum by 95% and that of M. plumbeus by 91%. Also, p-acetamide and MPAEMA had a scavenging effect on free radicals. According to results of the in silico analysis, the antimicrobial effect of these compounds is due to their effect on DNA ligase. Based on drug-likeness analysis, they were found to be consistent with the Lipinski, Veber, or Ghose rule. p-Acetamide and MPAEMA may be used as drugs.

Investigation of the Therapeutic Effects of Palbociclib Conjugated Magnetic Nanoparticles on Different Types of Breast Cancer Cell Lines.

Introduction: Drug targeting and controlled drug release systems in cancer treatment have many advantages over conventional chemotherapy in terms of limiting systemic toxicity, side effects, and overcoming drug resistance. Methods and Results: In this paper, fabricating nanoscale delivery system composed of magnetic nanoparticles (MNPs) covered with poly-amidoamine (PAMAM) dendrimers and using its advantages were fully used to help the chemotherapeutic drug, Palbociclib, effectively reach tumors, specifically and stay stable in the circulation longer. In order to determine whether conjugate selectivity can be increased for the specific drug type, we have reported different strategies for loading and conjugation of Palbociclib to different generations of magnetic PAMAM dendrimers. The best method leading to the highest amount of Palbociclib conjugation was chosen, and the characterization of the Palbociclib conjugated dendrimeric magnetic nanoparticles (PAL-DcMNPs) were performed. In vitro pharmacological activity of the conjugation was demonstrated by measuring the cell viability and lactate dehydrogenase (LHD) release. Obtained results indicated that PAL-DcMNPs treatment of the breast cancer cell lines, leads to an increase in cell toxicity compared to free Palbociclib. The observed effects were more evident for MCF-7 cells than for MDA-MB231 and SKBR3 cells, considering that viability decreased to 30% at 2.5 µM treatment of PAL-DcMNPs at MCF-7 cells. Finally, in Palbociclib and PAL-DcMNPs treated breast cancer cells, the expression levels of some pro-apoptotic and drug resistance related genes were performed by RT-PCR analysis. Conclusion: Our knowledge indicates that the proposed approach is novel, and it can provide new insight into the development of Palbociclib targeting delivery system for cancer treatment.

Determination of the relationship between doxorubicin resistance and Wnt signaling pathway in HeLa and K562 cell lines.

Activation of the Wnt signaling in some types of cancer and its relation with chemotherapy resistance is a very interesting issue that has been emphasized in recent years. Although, it is known that increase in the activity of ß-catenin is important in blast transformation and drug resistance, the underlying mechanisms are still unclear. In this study, changes in the expression levels of 186 genes that are thought to be important in drug resistance and Wnt signaling pathways were determined by using qPCR method in doxorubicin-sensitive and -resistant HeLa and K562 cell lines. It has been observed that the genes involved in the Wnt signaling pathways are involved in more changes in HeLa/Dox cells (36 genes) than in the K562/Dox cells (17 genes). Genes important for the development of cancer resistance have been found to be significantly different in expression levels of 18 genes in HeLa/Dox cells and 20 genes in K562/Dox cells. In both cell lines, the expression of ABCB1 gene was significantly increased to 160 and 103 fold, respectively. However, despite the resistance to same drug in HeLa and K562 cell lines, it appears that the expression levels of different oncogenes and genes involved in Wnt signaling pathways have been altered. It has been found that although resistance develops to the same drug in both cell lines, the expression levels of different genes have changed. If functional analysis of these genes is performed on patient population groups, these molecules may become candidates for novel therapeutic target molecules.