Novel Structures of Functionalized Graphene Oxide with Hydrazide: Characterization and Bioevaluation of Antimicrobial and Cytocompatibility Features

Graphite was oxidized to graphene oxide and activated by thionyl chloride, for further covalently linking three hydrazides with potential biological activity. The obtained materials were characterized by scanning electron microscopy with energy dispersive spectroscopy, Fourier-transform infrared and Raman spectroscopies. The presence of various functional groups specific to graphene oxide (GO) functionalized with different hydrazides was confirmed by spectral data. The ratio between D- and G-bands, observed in Raman spectra, allowed for an evaluation of the disorder degree and the mean crystallite size of the samples. The micrographs highlighted that the samples lead to the occurrence of disorders, probably caused by the sp3 carbons, the formation of oxygen-containing functional groups in the basal planes, and by various structural defects. The new graphene oxide–hydrazide derivatives were tested for their antimicrobial and cytotoxicity activity. Their antimicrobial activity against planktonic and biofilm-embedded cells was inferior to that of free hydrazides, except for GO-3 against planktonic Escherichia coli and GO-2 against Pseudomonas aeruginosa biofilm, demonstrating that further optimization is needed to be able to exploit the huge potential of GO for developing potent antimicrobials.

2-Oxoquinoline Arylaminothiazole Derivatives in Identifying Novel Potential Anticancer Agents by Applying 3D-QSAR, Docking, and Molecular Dynamics Simulation Studies

Tubulin plays an indispensable role in regulating various important cellular processes. Recently, it is known as a hopeful therapeutic target for the rapid division of cancer cells. Novel series of 2-oxoquinoline arylaminothiazole derivatives have been recently identified as promising tubulin inhibitors with potent cytotoxicity activity against HeLa cancer cell line. In this study, a 3D-QSAR approach by using CoMFA and CoMSIA techniques was applied to the reported derivatives to understand their pharmacological essentiality contributing to the tubulin inhibition activity and selectivity. The optimum CoMFA and CoMSIA models were found to have significant statistical reliability and high predictive ability after internal and external validation. By analyzing the contour maps, the electrostatic and hydrophobic interactions were found to be crucial for improving the inhibitory activity and four novel tubulin inhibitors (Compounds D1, D2, D3, and D4) were designed based on the validated 3D-QSAR models. Moreover, the docking findings showed that residues Gln136, Val238, Thr239, Asn167, Val 318 and Ala 316 played important roles for quinoline binding to tubulin. Among the newly designed compounds, compound D1 with the highest total scoring was subjected to detailed molecular dynamics (MD) simulation and compared to the most active compound. The conformational stability of compound D1 complexed with tubulin protein was confirmed by a 50-ns molecular dynamics simulation, which was congruent with molecular docking. Resumen. La tubulina juega un papel indispensable en la regulación de varios procesos celulares importantes. Recientemente, se le ha reconicodo como un agente promisorio para atacar la rápida división de las células cancerosas. Últimamente se ha identificado una nueva serie de derivados de arilaminotiazo-2-oxoquinolina como potenciales inhibidores de la tubulina, con una elevada actividad citotóxica contra la línea celular de cáncer HeLa. En este estudio, se aplicó a los derivados informados un estudio 3D-QSAR mediante el uso de técnicas CoMFA y CoMSIA para comprender los factores farmacológicos que contribuyen a la actividad como inhibidor y selectivo de la tubulina. Se encontró que los modelos CoMFA y CoMSIA óptimos tienen una confiabilidad estadística significativa y una alta capacidad predictiva después de la validación interna y externa. Al analizar los mapas de contorno, se descubrió que las interacciones electrostáticas e hidrófobas eran cruciales para mejorar la actividad inhibidora y se diseñaron cuatro nuevos inhibidores de la tubulina (compuestos D1, D2, D3 y D4) basados en los modelos 3D-QSAR validados. Además, los hallazgos de acoplamiento mostraron que los residuos Gln136, Val238, Thr239, Asn167, Val 318 y Ala 316 desempeñaron papeles importantes en la unión de la quinolina a la tubulina. Entre los compuestos de nuevo diseño, el compuesto D1 con la puntuación total más alta se sometió a una simulación detallada de dinámica molecular (MD) y se comparó con el compuesto más activo. La estabilidad conformacional del compuesto D1 unido a la proteína tubulina se confirmó mediante una simulación de dinámica molecular de 50 ns, que fue congruente con el acoplamiento molecular.

Cytotoxic Effect of Pterocarpus santalinus and stevia-based Mouthwash - A Lab-based Analysis

Introduction: Red sandalwood called as Pterocarpus santalinus is esteemed for the rich red colour of its wood. Pterocarpus santalinus used as astringent, analgesic and anti-inflammatory agent. Also helpful in treating skin illness, fistula, haemorrhage and ulcers. Stevia rebaudina is a food additive with lingering flavor. The wood isn't aromatic. The tree isn't to be mistaken for the fragrant Santalum sandalwood trees that fill locally in South India. In the present study we have prepared Pterocarpus santalinus and stevia-based mouthwash and evaluated its cytotoxic activity. Materials and Methods: 1g of Pterocarpus santalinus and stevia were measured and 50 ml of distilled water were measured. Both were mixed together to make the aqueous extract. To that 10 nauplii were slowly added and the cytotoxic activity is analysed by the number of live nauplii counts. Results: First day, Nauplii were grown in the medium and it hatches out after 24 hours. Second day, Mouthwash was added according to the concentration. Nauplii were collected and for each concentration 10 nauplii were added. After adding the nauplii, cytotoxicity well as undisturbed for one full day to analyze the inhibition of growth. Third day, nauplii were counted and cytotoxicity of mouthwash was evaluated. Statistical analysis showed significant reduction in the nauplii count (P<0.05). Conclusion: Medicinal plants cure many severe diseases. Application of medicinal plants in the field of medicine should be improved. Based on the results recorded in the present study, it is concluded that Pterocarpus santalinus has a potential cytotoxicity activity. Hence the present study findings provide a beautiful base for some of the medicinal uses of Pterocarpus santalinus.

Involvement of P-gp on Reversing Multidrug Resistance Effects of 23-Hydroxybetulinic Acid on Chemotherapeutic Agents

Betulinic acid (BA) and 23-Hydroxybetulinic acid (23-HBA) are natural products with similar structures, which show a range of biological effects including cytotoxicity activity. The aim of current research was to investigate and evaluate the combinational cytotoxicity of BA and 23-HBA with chemotherapeutic agents in vitro, and to clarify the potential interaction and related mechanism with P-gp. Instead of BA, 23-HBA could increase cytotoxicity of MCF-7/ADR cells to adriamaycin (ADR) and vincristine (VCR). The intracellular accumulation of ADR/VCR in MCF-7/ADR cells was obviously increased in the presence of 23-HBA. Furthermore, 23-HBA could show dose-dependent increase on the transport of VCR and digoxin, which are typical P-gp substrates, in both MDCK-MDR1 and Caco-2 cells. However, the transport of BA and 23-HBA was not influenced by P-gp inhibition in MDCK-MDR1 cells. MDR1 shift assay and molecular docking model suggested that both compounds showed interaction with P-gp, yet the binding affinity and sites are different. In conclusion, 23-HBA could strongly improve the efficacy of anti-tumor agents in multidrug resistance (MDR) cells, which was related to P-gp inhibition. The MDR1 shift assay and molecular docking study further revealed that 23-HBA and BA showed different interaction modes with P-gp.

The Emerging Role of Metformin in the Prevention and Treatment of Colorectal Cancer: A Game Changer for Management of Colorectal Cancer

: Metformin is an old, inexpensive and relatively safe anti-diabetic medication which can decrease the increased risk of several types of cancer in patients with diabetes. Recent meta-analyses revealed that metformin markedly decreased the incidence of colorectal adenoma, advanced adenoma and colorectal cancer (CRC) among patients with diabetes. Potential mechanisms by which metformin may decrease colorectal cancer risk include its effects on ameliorating intestinal inflammation and dysbiosis, suppressing major proliferative pathways, preventing DNA replication, accelerating tumor cells apoptosis, inhibiting intra-tumor angiogenesis and epithelial-mesenchymal transition (EMT), increasing tumor-infiltrating lymphocytes and CD68+ tumor-associated macrophages, and enhancing T cell cytotoxicity activity. It was uncovered that metformin can improve overall survival and CRC-specific survival among patients with diabetes and CRC. Interestingly, metformin decreased the incidence of colonic adenoma in patients with acromegaly and reduced the incidence of inflammatory bowel disease (IBD) among patients with diabetes, which can indirectly lower the risk of CRC. Results of phase II clinical trials revealed that metformin can enhance the anti-cancer effects of chemotherapeutic agents, such as 5-Fluorouracil (5-FU) and irinotecan on refractory CRC. Furthermore, metformin decreased the risk of new polyps and adenomas in patients without diabetes. Regarding the results of previous preclinical and clinical studies, it is rational to assess the effect of metformin in normoglycemic patients with CRC and expand its clinical application for treating CRC or preventing it in a high-risk population.

Potato Peels Mediated Synthesis of Cu(II)-nanoparticles from Tyrosinase Reacted with bis-(N-aminoethylethanolamine) (Tyr-Cu(II)-AEEA NPs) and Their Cytotoxicity against Michigan Cancer Foundation-7 Breast Cancer Cell Line

The synthesis of nanoparticles is most important in the context of cancer therapy, particularly copper nanoparticles, which are widely used. In this work, copper(II)-tyrosinase was isolated from potato peel powder. Copper nanoparticles (Tyr-Cu(II)-AEEA NPs) were synthesized via the reaction of tyrosinase with N-aminoethylethanolamine to produce Cu(II)-NPs and these were characterized by means of FT-IR, UV-Spectroscopy, XRD, SEM, TEM and a particle size analyzer. These Tyr-Cu(II)-AEEA NPs were tested as anticancer agents against MCF-7 breast cancer cells. Fluorescence microscopy and DNA fragmentation were also performed, which revealed the inhibiting potentials of Cu(II)-AEEA NPs and consequent cell death; Tyr-Cu(II)-AEEA NPs show potential cytotoxicity activity and this nano material could be contemplated as an anticancer medicament in future investigations.

Bioassay-Guided Discovery of Potential Partial Extracts with Cytotoxic Effects on Liver Cancer Cells from Vietnamese Medicinal Herbs

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and is the leading cause of cancer mortality in Vietnam. Our study aims to discover the partial extracts with the potential cytotoxic effects on HCC cells from the different parts of 24 Vietnamese medicinal plants traditionally used in liver cancer treatment. Out of 52 crude methanol extracts, we found that Luvunga scandens leaves, Hyptis suaveolens roots, and Solanum torvum leaves showed the notable cytotoxic effects against HCC cells. After that, we carried out partial extract of the three methanol extracts with ethyl acetate, water, n-hexane, and 90% methanol. The cytotoxic activity on Huh-7 HCC cells, antioxidant capacity, and total flavonoids content (TFC) of each partial extraction were determined. Methanol, ethyl acetate, and 90% methanol extracts showed moderate to strong cytotoxicity activity against Huh-7 HCC cells. Notably, the ethyl acetate and 90% methanol extract from H. suaveolens roots with high TFC values and strong antioxidant capacity could be promising sources of novel therapeutic modalities for HCC treatment. For the leaves of L. scandens and S. torvum, the ethyl acetate extract showed high TFC value and promising anti-HCC activity, therefore recommended further studies.

Antioxidant, Cytotoxic and larvicidal Potential in Oxalis latifolia Kunth. Methanolic Leaf Extract

Aims: The current work was analyzed in antioxidants, cytotoxicity and larvicidal potential were examined for O. latifolia methanolic leaf extract. Methodology: Antioxidant assasy for Hydroxyl radical (H2O2). Cytotoxicity potential was studied against colon (HT-29). Culex quinquefasciatus (IVth instar) larvae was used for larvicidal test. Results: Antioxidant and cytotoxicity exhibits significant activities with IC50 value of 442.94 µg/mL and also the cytotoxicity activity IC50 values of 50.00μg/mL for HT-29. Larval mortality against the larvae of Cx. quinquefasciatus showed best activity with LC50 09.50mg/L and LC90 28.72 mg/L. Conclusion: Thus, this study proved that methanolic leaf extracts of O. latifolia have significant biological activities. Hence, it can be used for pharmacetutical applications.