Eco-friendly synthesis of Ag/ZnO nanocomposite using Coleus amboinicus: Structural characterization and evaluation of antibacterial and anticancer activities

ABSTRACTObjective: This study was undertaken to know about the antibacterial and anticancer activity of synthesized zinc oxide (ZnO) nanoparticles (NPs).Methods: The ZnO NPs and different concentration of Ce3+ (0.05M, 0.10M, and 0.15M)-doped ZnO NPs were synthesized by coprecipitation method.The synthesized nanoparticles were analyzed by X-ray diffraction (XRD) and HRSEM. The antibacterial studies were performed against a set ofbacterial strains as Gram-positive bacteria (Streptococcus aureus and Streptococcus pneumonia) and Gram-negative (Escherichia coli, Pseudomonasaeruginosa, Proteus vulgaris, Klebsiella pneumonia, and Shigella dysenteriae) bacteria. The cytotoxic effect of ZnO and Ce-doped ZnO was analyzed incultured (A549) human lung cancer cell line.Result: The XRD studies showed the wurtzite structure of nanoparticles. HRSEM analysis showed the spherical shape of ZnO and Ce-doped ZnO. TheZn0.85Ce0.15O NPs possessed more antibacterial effect as compared to the other ZnO and Ce-doped ZnO NPs. The Zn0.90Ce0.10O NPs created the highestcytotoxicity activity. With respect to cell death, as low a concentration of 68±0.05 μg/ml of Zn0.90Ce0.10O NPs was good enough to cause loss of viabilityof 50% of the cell as compared to ZnO and Zn1-xCexO (x=0.05 and 0.15) NPs.Conclusion: Results from this work concluded that Zn0.85Ce0.15O and Zn0.90Ce0.10O NPs possess antibacterial and anticancer activity, respectively.Keywords: Zinc oxide nanoparticles, Coprecipitation method, Antibacterial activity and anticancer activity, Human lung cancer cell line.

Titanium dioxide nanoparticles exhibit good anticancer and antibacterial activities. They are known to be environmentally friendly, stable, less toxic, and have excellent biocompatibility nature. Due to these properties, they are well suited for biological applications particularly in biomedical applications such as drug delivery and cancer therapy. In this research article, three medicinal herbs namely, Plectranthus amboinicus (Karpooravalli), Phyllanthus niruri (Keezhanelli), and Euphorbia hirta (Amman Pacharisi), were used to modify the surface of the TiO2 nanoparticles. The synthesized nanoparticles were subjected to various characterization techniques. The samples are then subjected to MTT assay to determine cell viability. KB oral cancer cells are used for the determination of the anticancer nature of the pure and bio modified nanoparticles. It is observed that Plectranthus amboinicus-Phyllanthus niruri modified TiO2 nanoparticles exhibit excellent anticancer activities among other bio modified and pure samples. The samples are then examined for antibacterial activities against three Gram-negative bacterial strains namely, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and two Gram-positive bacterial strains namely, Staphylococcus aureus and Streptococcus mutans, respectively. Among the modified and pure samples, Plectranthus amboinicus showed good antibacterial activity against Gram-positive and Gram-negative bacteria. In the Flow cytometry analysis, the generation of p53 protein expression from Plectranthus amboinicus-Phyllanthus niruri modified TiO2 nano herbal particles shows the anti-cancerous nature of the sample. Then to determine the toxic nature of the Plectranthus amboinicus-Phyllanthus niruri modified TiO2 nano herbal particles against normal cells, the NPs were subjected to MTT assay against normal L929 cells, and it was found to be safer and less toxic towards the normal cells.

ZnO nanoparticles (NPS) with different morphologies were synthesized, and the antibacterial and anticancer activity was studied, herein. The physicochemical characterization was carried out by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR) and UV-visible. To study the antibacterial and anticancer capability of ZnO NPS, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria and HeLa cancer cells were exposed at different doses of ZnO NPS (7-250µg/mL). TEM analysis confirmed the obtention of spherical, hexagonal and rod ZnO NPS with an average diameter of 20 ± 4nm, 1.17 ± 0.3µm and 1.11 ± 1.2µm, respectively. XRD diffractograms showed the characteristic pattern of crystalline ZnO in wurtzite phase. FTIR and UV-vis spectra showed slight differences of the main absorption peaks, revealing that different ZnO NPS morphologies may cause shifts in spectra. Biological essays showed that the number of E. coli and S. aureus bacteria as well as HeLa cells decreases linearly by increasing the nanoparticle concentration. However, the best anticancer and antibacterial activity was shown by spherical ZnO NPS at 100µg/mL. The better capability of spherical ZnO NPS than hexagonal and rod ZnO NPS is related with its small particle size. The present results suggest that the spherical ZnO NPS has a great potential as an antibacterial and anticancer agent.

Cancer remains the leading cause of death globally, with breast cancer being the foremost cause among women and lung cancer ranking second for both women and men. This study aimed to identify the metabolomic content of Coleus amboinicus leaves and evaluate their anticancer activities against breast and lung cancer cells, thereby providing insights into potential alternative treatments for these cancers and initiating research on active isolates from C. amboinicus leaves. The research methodology involved maceration using ethanol, followed by multistage partitioning with solvents n-hexane, chloroform, and ethyl acetate. Phytochemical screening was performed using standard reagents to detect the presence of alkaloids, phenolics, polyphenols, flavonoids, steroids/triterpenoids, and saponins. Metabolomic profiling was conducted using LC/HRMS, and the anticancer activities against lung cancer cells (A549) and breast cancer cells (MCF-7) were assessed using the MTT assay. The results showed that the C. amboinicus extract contains various secondary metabolite groups such as alkaloids, phenolics and polyphenols, flavonoids, steroids, triterpenoids, and saponins. The diverse metabolomic profile of the C. amboinicus leaf extract demonstrated potential activity against cancer, as evidenced by in vitro tests on lung (A549) and breast (MCF-7) cancer cells. C. amboinicus leaf extract shows promise as an active ingredient in the prevention and alternative natural treatment of lung and breast cancer. Further research and testing, both in vivo and clinically, are warranted.

Hepatocellular carcinoma (HCC) is an aggressive form of cancer, with high rates of morbidity and mortality, a poor prognosis and limited therapeutic options. The objective of the present study was to demonstrate the anticancer activity of oleanolic acid in HepG2 human HCC cells. Cell viability was evaluated using an MTT assay, following administration of various doses of oleanolic acid. The effect of oleanolic acid on cell cycle phase distribution and mitochondrial membrane potential was evaluated using flow cytometry with propidium iodide and rhodamine-123 DNA-binding cationic fluorescent dyes. Fluorescence microscopy was employed to detect morphological changes in HepG2 cells following oleanolic acid treatment. The results revealed that oleanolic acid induced a dose-dependent, as well as time-dependent inhibition in the growth of HepG2 cancer cells. Following acridine orange and ethidium bromide staining, treatment with various doses (0, 5, 25 and 50 µM) of oleanolic acid induced typical morphological changes associated with apoptosis, including cell shrinkage, membrane blebbing, nuclear condensation and apoptotic body formation. Cell cycle analysis revealed that oleanolic acid induced cell cycle arrest in HepG2 cells at the sub-G1 (apoptotic) phase of the cell cycle, in a dose-dependent manner. Staining with Annexin V-fluorescein isothiocyanate and propidium iodide revealed that apoptosis occurred early in these cells. Oleanolic acid treatment also resulted in fragmentation of nuclear DNA in a dose-dependent manner, producing the typical features of DNA laddering on an agarose gel. The results also demonstrated that oleanolic acid treatment resulted in a potent loss of mitochondrial membrane potential, which also occurred in a dose-dependent manner. Therefore, oleanolic acid may be used as a therapeutic agent in the treatment of human HCC.

Background: Plectranthus amboinicus (Lour.) Spreng is a plant that has a high flavonoid content. The leaves of Plectranthus amboinicus (Lour.) Spreng contain many flavonoids Chrysoeriol, Cirsimaritin, Eriodictyol, Luteolin, Rutin, Salvigenin, Thymoquinone, Quercetin, Apigenin, and 5-O-Methyl-Luteolin. Objectives: To determine the antioxidant activity and anticancer activity of flavonoid compounds contained in Plectranthus amboinicus (Lour.) Spreng. Methods: Anticancer activity testing was carried out by in silico against several cancer receptors and antioxidant activity testing was carried out by in vitro using the 1,1-Diphenyl-2-Picryhydrazil method. The results showed that the flavonoid compounds contained in Plectranthus amboinicus (Lour.) Spreng have similar anticancer activity to the reference molecule at the P-Glycoprotein-1, Cyclin Dependent Kinase-2, and Phosphoinositide-3-Kinase receptors, as well as better anticancer activity than the reference molecule for the Cyclooxygenase-2 and Phosphoenolpyruvate Carboxykinase receptors. Results: The antioxidant activity of the extract gave an Inhibitory Concentration 50% value of 9.77 g/mL, the flavonoid compounds contained in Plectranthus amboinicus (Lour.) Spreng gave an Inhibitory Concentration 50% value that lower than the extract, which ranged from 6.92 g/mL to 8.50 g/mL. Flavonoids in Plectranthus amboinicus (Lour.) Spreng anticancer activity by in silico molecular docking and antioxidant activity by in vitro 1,1-Diphenyl-2-Picryhydrazil method. Conclusions: All the flavonoid compounds contained in the ethanolic extract of Plectranthus amboinicus (Lour.) Spreng leaves exhibit very strong anti-cancer and antioxidant activity, which results in ethanolic extract of Plectranthus amboinicus (Lour.) Spreng leaves have very strong antioxidant activity.

The unique physicochemical properties of cupric oxide nanoparticles (CuO NPs) make them suitable for a wide range of therapeutic applications. Here, we synthesized β-cyclodextrin (βCD) capped CuO NPs (CuONPs@βCD) using a simple reduction process. The formation and physicochemical characteristics were identified via different spectroscopic techniques. The CuONPs@βCD displayed antimicrobial activity as good as commercial drugs. Dimethyl thiazolyl tetrazolium bromide (MTT) assay was carried out to assess the anticancer properties of CuONPs@βCD against A549 lung cancer cells. The result demonstrated that the anticancer activity of CuONPs@βCD with IC50 values of 41.06 ± 0.05 and 19.46µg/mL at 24 and 48-h incubation period, respectively. CuONPs@βCD exhibited anticancer activity on A549 lung cancer cells while having less adverse effects on normal cells. Annexin V-FITC/PI assay, reactive oxygen species (ROS) analysis, disruption of mitochondrial membrane potential (Δψm), and AO/EB apoptosis studies in A549 cells revealed significant apoptotic impact of CuONPs@βCD when compared to the control. Moreover, thermal therapy study of CuONPs@βCD in lung tumor using COMSOL Multiphysics has been reported. Our investigation revealed Case III, where the temperature distribution at the top surface of the tumor is best and may be the most effective way to treat lung cancer. It was found that an incident flux of 8000 Wm- 2 for 900s and an extinction coefficient of 8.266m- 1 for CuONPs@βCD were the best conditions for reaching a temperature of 43.63 °C across the whole tumor area. Thus, these findings open new research opportunities and potential use of CuONPs@βCD for biological applications.

Synthesis of zinc oxide nanoparticles (ZnONPs) by an ecological approach using Streptomyces sp. as reducing agent is reported. ZnONPs were synthesized from aqueous zinc chloride solution by cell-free supernatant of a novel isolate. Hyperchromic shift was observed at 364 nm using UV–visible spectroscopy and also by the naked eye as a color change from dark green to milk white. Evidence for proteins acting as reducing and capping agent was obtained by Fourier-transform infrared spectroscopy. From the X-Ray diffraction studies, the lattice planes and obtained peak positions confirmed the hexagonal close-packed crystalline structure of ZnONPs. Surface topographical studies revealed that the biosynthesized ZnONPs had spherical shape with mean diameter of about 20–50 nm. Transmission electron microscopy revealed that the nanoparticles had spherical structure with uniform distribution along the surface. The anticancer activity of the synthesized nanoparticles was evaluated against A549 lung cancer cells, and their antibacterial activity against Escherichia coli and Bacillus subtilis was analyzed and reported.

Green biosynthesis of selenium and zinc oxide nanoparticles using whole plant extract of Rheum ribes: Characterization, anticancer, and antimicrobial activity

Pyrimidines have widespread activity and have shown potent antibacterial and anticancer activity. To synthesise a range of pyrimidine diones and test them for their antibacterial and anticancer activity. The pyranopyrimidin-2,4-dione derivatives (1-7) were synthesized in a one-pot reaction by reacting malononitrile and barbituric acid with several aromatic aldehydes in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) in aqueous medium. The compounds were tested for their antibacterial activity using the broth microdilution method and for their cytotoxicity against three cell lines, HeLa (cervical cancer), Caco-2 (human colon adenocarcinoma) and HEK 293 (human embryonic kidney cells) using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) assay. Compounds 1-7 were successfully synthesized in yields of >90%. The 3,4-dihydroxyaryl (3) and the 2,5- dimethoxyaryl (7) derivatives were novel. Compounds 3, 5 (4'-methoxy derivative) and 6 (2',3'-dimethoxy derivative) showed antibacterial activity comparable to or better than the standard ampicillin. All the test compounds 1-7 showed good anticancer activity. The IC50 values ranged from 3.46 to 37.13 μM (HeLa); 136.78 to 297.05 μM (Caco-2) and 137.84 to 333.81 μM (HEK293). The best activity was seen in the HeLa cell line when compared to the standard 5FU (5-Fluorouracil IC50 of 41.85 μM), with 1, 2, 5 and 7 having IC50 values of 10.64, 3.46, 4.36 and 4.44 μM respectively. Additionally, two representative compounds (1 and 7) found to be potent against the two cell lines (HeLa and HEK 293) were docked into the binding site of human kinesin Eg5 with the aim of predicting their binding propensities and to establish their mechanism of action. The Lipinski parameters of these compounds were also computed and analysed for their drug-likeness. Compound 6 is an excellent candidate for a broad spectrum antibiotic with MBCs of 45.6-365.2 μM, while both 3 and 6 have the potential to be developed into an antibiotic against MRSA, with MBCs of 183-199 μM. Since all synthesized compounds showed IC50 values of 10 μM or less especially against the HeLa cells, they can be considered good lead compounds for anticancer agents. Additionally, the docking simulations suggested a good binding affinity of the compounds with Eg5 and indicated their anti-cancer action, at least partially, through its inhibition. The predicted Lipinski descriptors also indicated the potential of these compounds as an orally active drug.

Three 8-hydroxyquinoline-stabilized hafnium complexes, [HfIV(oxinate)4], were synthesized with good aqueous stability and solubility by reacting HfIVCl4 with 8-hydroxyquinoline (HL1), 2-methyl-8-hydroxyquinoline (HL2) and 5-chloro-8-hydroxyquinoline (HL3) in THF, achieving high yields. Among the synthesized complexes, [HfIV(L1)4] and [HfIV(L3)4] exhibited potent inhibitory activity against human liver (Hep G2), cervical (HeLa S3) and lung (PC9) cancer cell lines, while showing low toxicity against non-tumorigenic murine epithelial AML12 cells. Notably, [HfIV(L1)4] demonstrated the most potent activity, with an IC50 value of 0.8±0.3μM against Hep G2 cells, which is 17 times lower than that of cisplatin (IC50=13.8±1.3 μM). Mechanistic cell studies revealed that [HfIV(L1)4] could effectively inhibit cell migration, induce reactive oxygen species generation and cause mitochondrial membrane potential disruption. Furthermore, [HfIV(L1)4] blocked the cell cycle progression at the G2/M phase and led almost exclusively to early apoptosis in Hep G2 cells. Western blot analysis revealed that in Hep G2 cells [HfIV(L1)4] could upregulate the expression of caspase-3 and Bax proteins while downregulating the expression of the anti-apoptotic Bcl-2 protein, highlighting the apoptotic pathway as a key mechanism of action. Comparisons are made with previously reported [ZrIV(L1)4], which shows higher cytotoxicity, cellular uptake, reactive oxygen species generation, mitochondrial damage and stronger inhibition of antioxidant enzymes' activity. However, [HfIV(L1)4] induces primarily early apoptosis, which is advantageous. Overall, these rare earth complexes, particularly [HfIV(L1)4] and [ZrIV(L1)4], demonstrate promising potential as novel anticancer agents with significant efficacy against human liver cancer cells and favourable selectivity profiles for further therapeutic development.

Numerous in vitro and in vivo studies have demonstrated that calcitriol [1,25(OH)2D3] and different vitamin D analogs possess antineoplastic activity, regulating proliferation, differentiation and apoptosis, as well as angiogenesis. Vitamin D compounds have been shown to exert synergistic effects when used in combination with different agents used in anticancer therapies in different cancer models. The aim of this study was to evaluate the mechanisms of the cooperation of the vitamin D compounds [1,24(OH)2D3 (PRI-2191) and 1,25(OH)2D3] with tyrosine kinase inhibitors (imatinib and sunitinib) together with cytostatics (cisplatin and docetaxel) in an A549 non-small cell lung cancer model. The cytotoxic effects of the test compounds used in different combinations were evaluated on A549 lung cancer cells, as well as on human lung microvascular endothelial cells (HLMECs). The effects of such combinations on the cell cycle and cell death were also determined. In addition, changes in the expression of proteins involved in cell cycle regulation, angiogenesis and the action of vitamin D were analyzed. Moreover, the effects of 1,24(OH)2D3 on the anticancer activity of sunitinib and sunitinib in combination with docetaxel were examined in an A549 lung cancer model in vivo. Experiments aiming at evaluating the cytotoxicity of the combinations of the test agents revealed that imatinib and sunitinib together with cisplatin or docetaxel exerted potent anti-proliferative effects in vitro on A549 lung cancer cells and in HLMECs; however, 1,24(OH)2D3 and 1,25(OH)2D3 enhanced the cytotoxic effects only in the endothelial cells. Among the test agents, sunitinib and cisplatin decreased the secretion of vascular endothelial growth factor (VEGF)-A from the A549 lung cancer cells. The decrease in the VEGF-A level following incubation with cisplatin correlated with a higher p53 protein expression, while no such correlation was observed following treatment of the A549 cells with sunitinib. Sunitinib together with docetaxel and 1,24(OH)2D3 exhibited a more potent anticancer activity in the A549 lung cancer model compared to double combinations and to treatment with the compounds alone. The observed anticancer activity may be the result of the influence of the test agents on the process of tumor angiogenesis, for example, through the downregulation of VEGF-A expression in tumor and also on the induction of cell death inside the tumor.

We, herein, report the synthesis, characterization, luminescence properties, anticancer, and antibacterial activities of a family of novel half-sandwich iridium(III) complexes of the general formula [(η5-Cpx)Ir(C^N)Cl]PF6- [Cpx = pentamethylcyclopentadienyl (Cp*) or tetramethyl(biphenyl)-cyclopentadienyl (Cpxbiph)] bearing versatile imine-N-heterocyclic carbene ligands. In this complex framework, substituents on four positions could be modulated, which distinguishes this class of complex and provides a large amount of flexibility and opportunity to tune the cytotoxicity of complexes. The X-ray crystal structures of complexes 4 and 10 exhibit the expected "piano-stool" geometry. With the exception of 1, 2, and 11, each complex shows potent cytotoxicity, with IC50 (half-maximum inhibitory concentration) values ranging from 1.99 to 25.86 μM toward A549 human lung cancer cells. First, the effect of four positions bearing different substituents in the complex framework on the anticancer activity, that is, structure-activity relationship, was systematically studied. Complex 8 (IC50 = 1.99 μM) displays the highest anticancer activities, whose cytotoxicity is more than 10-fold higher than that of the clinical platinum drug cisplatin against A549 cancer cells. Second, their chemical reactivity including nucleobases binding, catalytic activity in converting coenzyme NADH to NAD+, reaction with glutathione (GSH), and bovine serum albumin (BSA) binding is investigated. No reaction with nucleobase is observed. However, these iridium(III) complexes bind rapidly to GSH and can catalyze oxidation of NADH to NAD+. In addition, they show moderate binding affinity to BSA and the fluorescence quenching of BSA by the iridium (III) complexes is due to the static quenching. Third, the mode of cell death was also explored through flow cytometry experiments, including cell cycle, apoptosis induction, reactive oxygen species (ROS) and mitochondrial membrane potential. It seems that cell cycle perturbation, apoptosis induction, increase of ROS level and loss of mitochondrial membrane potential together contribute to the anticancer potency of these complexes. Last, the use of confocal microscopy provides insights into the microscopic mechanism that the typical and most active complex 8 enters A549 lung cancer cells mainly through energy-dependent pathway and is located in lysosome. Furthermore, lysosome damage and nuclear morphology were detected by confocal microscopy. Nuclear condensation and apoptotic bodies may finally induce cells apoptosis. Interestingly, complex 8 also shows antibacterial activity against Gram-positive Staphylococcus aureus. This work may provide an alternative and effective strategy to smart design of potent organometallic half-sandwich iridium(III) anticancer drugs.

Gelatin composite gel particles comprised of in-situ formed zinc oxide and silver nanoparticles with enhanced antibacterial activities via enzymatic degradation

Our previous study demonstrated that thiophene-substituted synthetic curcumin analogs possessed better antibacterial activity and stability than natural curcumin, demethoxycurcumin, or bisdemethoxycurcumin in antibacterial photodynamic therapy (aPDT). In addition, the activity of the furan-substituted analogs was weaker than that of the thiophene-substituted compounds. As oxygen, sulfur, and selenium belong to the same group in the periodic table, the antibacterial and anticancer activities of these three different elemental analogs were compared and investigated. The thiophene-substituted analog (compound 3) exhibited the most potent antibacterial activity in aPDT experiments. However, the furan-substituted analog (compound 1) exhibited the most potent anticancer activity. These results indicate that the differences in atomic radii or energy levels in these compounds produce different cell-attack results on generated free radicals. Ruthenium(II) complexes have a good reputation for use in PDT for cancer treatment. Our results show that complexation of ruthenium(II) with thiophene-substituted curcumin analogs does not enhance their antibacterial or anticancer activity.