A549 Human Cancer Cells Research Articles

Synthesis of 1-(2-Hydroxyphenyl)- and (3,5-Dichloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic Acid Derivatives as Promising Scaffolds for the Development of Novel Antimicrobial and Anticancer Agents.

Increasing antimicrobial resistance among Gram-positive pathogens and pathogenic fungi remains one of the major public healthcare threats. Therefore, novel antimicrobial candidates and scaffolds are critically needed to overcome resistance in Gram-positive pathogens and drug-resistant fungal pathogens. In this study, we explored 1-(2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid and its 3,5-dichloro-2-hydroxyphenyl analogue for their in vitro antimicrobial activity against multidrug-resistant pathogens. The compounds showed structure-dependent antimicrobial activity against Gram-positive pathogens (S. aureus, E. faecalis, C. difficile). Compounds 14 and 24b showed promising activity against vancomycin-intermediate S. aureus strains, and favorable cytotoxic profiles in HSAEC-1 cells, making them attractive scaffolds for further development. 5-Fluorobenzimidazole, having a 3,5-dichloro-2-hydroxyphenyl substituent, was found to be four-fold, and hydrazone, with a thien-2-yl fragment, was two-fold stronger than clindamycin against methicillin resistant S. aureus TCH 1516. Moreover, hydrazone, bearing a 5-nitrothien-2-yl moiety, showed promising activity against three tested multidrug-resistant C. auris isolates representing major genetic lineages (MIC 16 µg/mL) and azole-resistant A. fumigatus strains harboring TR34/L98H mutations in the CYP51A gene. The anticancer activity characterization demonstrated that the 5-fluorobenzimidazole derivative with a 3,5-dichloro-2-hydroxyphenyl substituent showed the highest anticancer activity in an A549 human pulmonary cancer cell culture model. Collectively these results demonstrate that 1-(2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid derivatives could be further explored for the development of novel candidates targeting Gram-positive pathogens and drug-resistant fungi.

Preparation and characterization of the farnesiferol C-loaded solid lipid nanoparticles decorated with folic acid-bound chitosan and evaluation of its in vitro anti-cancer and anti-angiogenic activities

Farnesiferol C (FC) has long been used as a cancer prevention agent. In the present study, FC was loaded into solid lipid nanoparticles (SLN) coated with folic acid (FA) bound chitosan (CS), FC-SLN-CS-FA, by homogenization followed by ultrasonication. Then its toxicity effect on cancer cells compared to normal cells was investigated by the MTT method. In the following, the pro-apoptotic effects of synthesized nanoparticles were evaluated by flow cytometry and acridine orange, propidium iodide, and DAPI staining, and the expression of genes involved in apoptosis was evaluated. The anti-oxidant effects of formulations have been evaluated using DPPH and ABTS assay. To investigate the anti-angiogenic effects of nanoparticles, the chicken chorioallantoic membrane (CAM) assay was used and the expression of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) genes was used by real-time quantitative PCR (qPCR). The formed nanoparticles with a size of 150 nm and a dispersion index of 0.30 had a surface charge of +17 mV. These nanoparticles exhibited significant growth and proliferation inhibitory effects in PANC, AGS, HT-29, MCF7, and A549 human cancer cells from the lowest concentration (15.6 µg/mL, *** p < 0.001). The flow cytometry analysis shows 10.1%, 48.8%, and 74.4% subG1 arrest at the concentrations of 6, 36, and 66 µg/mL of the FC-SLN-CS-FA, respectively. The formulation caused apoptotic cell death by 3-fold overregulating BAX at concentrations of 36 and 66 µg/mL, and 2- and 2.5-fold overexpression of caspase-9 at concentrations of 36 and 66 µg/mL respectively. The treatment with FC-SLN-CS-FA resulted in decreasing BCL2 and NF-κB gene expression. The ABTS and DPPH assays showed the anti-oxidant properties of formulation in a concentration-dependent manner. FC-SLN-CS-FA significantly inhibited angiogenesis in CAM by reducing the length and number of blood vessels. Considering the pro-apoptotic and anti-angiogenic effects of FC-SLN-CS-FA, it can be said that these nanoparticles can effectively suppress the carcinogenesis of multipotent cancer stem cells. Therefore, they have the potential to be studied as an efficient anticancer agent.

Design, synthesis, and antiproliferative properties of new 1,2,3-triazole-carboximidamide derivatives as dual EGFR/VEGFR-2 inhibitors

A new series of substituted aryl carboximidamide VIa-o was designed and synthesised. IR, 1H NMR, 13C NMR as well as elemental microanalysis were used to confirm the structures of the new compounds. The antiproliferative effect of the news compounds against four cancer cell lines was investigated. Compounds VIc, VIg, VIj, VIk, VIm, and VIo were the most potent ones with GI50 ranging from 34 to 48 nM, compared with erlotinib (GI50 of 33 nM). The utmost potent compounds were further examined for their efficacy as EGFR inhibitors, and the results showed that the tested compounds inhibited EGFR with IC50 ranging from 83 nM to 112 nM when compared to the reference erlotinib (IC50 = 80 nM). Moreover, the six most potent compounds had promising VEGFR-2 inhibitory activity, with IC50 ranging from 1.8 nM to 11.4 nM compared with sorafenib, (IC50 = 0.17 nM). The most potent VEGFR-2 inhibitors were VIc, VIk, and VIo, with IC50 2.90, 1.80, and 2.40 nM, respectively. Additionally, molecular docking simulations of the most potent compounds against EGFR and VEGFR-2 enzymes highlighted high binding affinity and active site interactions of compounds VIc, VIk, and VIo that could be shown as potential dual EGFR and VEGFR-2 inhibitors. The apoptotic mechanism displayed that the most active compound VIk showed the highest induced levels for Caspase-3 and Bax while down-regulated the anti-apoptotic Bcl-2 protein levels in the A-549 human epithelial cancer cell line. The ADME of compounds VIa-o revealed safety and good pharmacokinetic profile of active compounds.

Apoptotic effects of phenols from the twigs and leaves of Garcinia nujiangensis

In order to find potential agents for treating cancer disease in naturally occurring compounds, we conducted a systematic phytochemical investigation on the endemic species of Garcinia nujiangensis. Three new biphenyl derivatives (1–3) and one new polycyclic polyprenylated benzophenone (4), together with four known benzophenone analogues (5–8), have been isolated from the CH2Cl2 extract of the twigs and leaves of G. nujiangensis. Their structures were determined by detailed spectroscopic analyses and comparison with structurally related known analogues. Experimental and calculated ECD method was used to determine the absolute configuration of 1 and 4. Moreover, compounds 5–7 were isolated for the first time from this species. The cytotoxicities of the new compounds were evaluated using HL-60, HepG2, and A549 human cancer cell lines. Compound 4 showed more significant antiproliferative effects against HepG2 cells with an IC50 value of 11.38 ± 0.79 μM than that of three biphenyl derivatives. The morphological features of apoptosis were evaluated in 4-treated HepG2 cells. Compound 4 effectively prevented the cell cycle progression of HepG2 cells in G2 phase. Additionally, western blot analysis indicated that treatment of 4 on HepG2 cells led to decreased expression of anti-apoptotic Bcl-2 and pro-Caspase-3, and increased protein expression of both pro-apoptotic Bax and cleaved PARP with reference to β-actin. Overall, our results suggested that the active polycyclic polyprenylated benzophenone derivatives in the twigs and leaves of G. nujiangensis can be used as a valuable source of bioactive compounds for the pharmaceutical industry.

Anti-Inflammatory, Neurotrophic, and Cytotoxic Oxylipins Isolated from Chaenomeles sinensis Twigs

Oxylipins are important biological molecules with diverse roles in human and plants such as pro-/anti-inflammatory, antimicrobial, and regulatory activity. Although there is an increasing number of plant-derived oxylipins, most of their physiological roles in humans remain unclear. Here, we describe the isolation, identification, and biological activities of four new oxylipins, chaenomesters A-D (1-4), along with a known compound (5), obtained from Chaenomeles sinensis twigs. Their chemical structures were determined by spectroscopic (i.e., NMR) and spectrometric (i.e., HRMS) data analysis including 1H NMR-based empirical rules and homonuclear-decoupled 1H NMR experiments. Chaenomester D (4), an omega-3 oxylipin, showed a potent inhibitory effect on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells (NO production, 8.46 ± 0.68 μM), neurotrophic activity in C6 cells through the induction of the secretion of nerve growth factor (NGF, 157.7 ± 2.4%), and cytotoxicity in A549 human cancer cell lines (IC50 = 27.4 μM).

Growth Hormone-Releasing Hormone Antagonist JV-1-36 Suppresses Reactive Oxygen Species Generation in A549 Lung Cancer Cells.

Growth hormone-releasing hormone (GHRH) and its receptors are expressed in a variety of human cancers, and have been involved in malignancies. GHRH antagonists (GHRHAnt) were developed to suppress tumor progression and metastasis. Previous studies demonstrate the involvement of reactive oxygen species (ROS) in cancer progression. Herein, we investigate the effect of a commercially available GHRH antagonist, namely JV-1-36, in the redox status of the A549 human cancer cell line. Our results suggest that this peptide significantly reduces ROS production in those cells in a time-dependent manner and counteracts H2O2-induced ROS. Our study supports the anti-oxidative effects of JV-1-36 and contributes in our knowledge towards the in vitro effects of GHRHAnt in cancers.

Induction of apoptosis by ethanolic extract of leaf of Dillenia pentagyna Roxb. in A549 cells via NF-κB pathway

BackgroundA large number of populations worldwide still rely on crude extracts of different parts of medicinal plants. Different parts of Dillenia pentagyna has long been used in India for the treatment of different disorders. ObjectiveCytotoxic and apoptosis-inducing capability of ethanolic extract of leaves of Dillenia pentagyna (EELDP) were studied on various human cancer cell lines. MethodsCell viability and morphology, nuclear fragmentation, caspase-3 activation, ratio of Bax/Bcl2, NF-κB expression were measured in three human cancer cells A549, HeLa and U2OS after treatment with EELDP. Further, mitochondrial membrane potential, cell cycle analysis, ROS generation were done in A549 cells. ResultsEELDP dose-dependently increased cell cytotoxicity to all the human cancer cells but showed nontoxic to the normal lung cell L-132. EELDP (0–0.6 mg/ml) significantly induced the intrinsic pathway of apoptosis via fall in mitochondrial membrane potential leading to an increase in Bax to Bcl2 ratio, the release of cytochrome-c, caspase-3 activation, and nuclear fragmentation. EELDP significantly reduced NF-κB expression. However, combined EELDP with Bay11–7082 (NF-κB inhibitor) treatment significantly enhanced Bax to Bcl2 ratio and caspase-3 activation. ConclusionThis data implicates that EELDP has a strong potential to kill various aggressive human cancer cells by inducing apoptosis via NF- κB pathway.

Design, synthesis, anticancer activity of new amide derivatives derived from 1,2,3-triazole-benzofuran hybrids: An insights from molecular docking, molecular dynamics simulation and DFT studies

A new series of amide derivatives derived from 1,2,3-triazole-benzofuran hybrids (9a-j) have been synthesized and their structures were confirmed by using spectroscopic/analytical techniques. All the synthesized compounds were evaluated for their anticancer activity in four human cancer cell lines i.e.; PC3 (Prostate cancer), A549 (Lung cancer), MCF7 (Breast cancer), and A2780 (Ovarian cancer) by employing MTT assay using etoposide as the reference compound. In comparison to etoposide, all of the compounds showed good to moderate activity. The IC50 values of the novelamide derivatives (9a-j) rangedfrom 0.013 ± 0.0012 µMto 21.8 ± 8.52 µMwhereas positive control (etoposide) showed1.38 ± 0.56 µM to 3.08 ± 0.135 µM respectively. The developed amide derivatives of 1,2,3-triazole-benzofuran hybrids were found to be good alternative anticancer agents. Among the new amide derivatives (9a-j), mainly 9a-c, 9i, and 9j displayed highly potent anticancer activity towards MCF7 (9a, 9j), A549(9b), A2780(9c) and PC3(9i) human cancer cell lines respectively. Furthermore, using molecular docking simulations with the BCL-2 (PDB ID: 4LVT), Colchicine binding site of Tubulin (PDB ID: 1SA0), Kinase domain of C-ABL (PDB ID: 1IEP) and CLK-2 (PDB ID: 6FYL) proteins, the experimentally observed biological impact of new amide derivatives (9a-j) were investigated, and it was discovered that our experimental findings are consistent with the computationally derived results. Molecular docking predictions were further supported by MD simulation and DFT studies. The docking scores of the newly produced amide derivatives (9a-j) varied from -2.74 kcal/mol to -8.022 kcal/mol, indicating increased inhibitory actions. Human oral absorption is expected to be greater than 70%.

The Use of the QbD Approach to Optimize the Co-Loading of Simvastatin and Doxorubicin in Liposomes for a Synergistic Anticancer Effect.

The present study aimed to optimize a liposomal formulation co-encapsulating simvastatin (SIM) and doxorubicin (DOX) that has future perspectives in anticancer therapy. The optimization process was performed by implementing the Quality by Design concept and by considering the results of a previous screening study. Failure Mode and Effects Analysis was used for the identification of the potential critical factors, i.e., phospholipid, SIM and DOX concentration, which were assessed in an optimization experimental design with the purpose of designing an optimal formulation. The optimal formulation, meeting the established quality profile, was additionally characterized in terms of the release profile and antiproliferative effects. During dissolution studies, a novel chronoamperometric method was used for the simultaneous quantification of SIM and DOX. The obtained data confirmed the similarity of this method with a validated HPLC method. The anticancer potential of the optimal formulation was tested against two human cancerous cell lines, namely T47D-KBluc human mammary ductal carcinoma cell line and A549 human pulmonary cancer cell line. The results highlighted that the antiproliferative effect of the optimal formulation is concentration dependent and favors a synergistic effect of the two drugs.

Novel hybrid molecules based on disulfides and 1,2,4-triazole as antiproliferative agents

A series of novel hybrid molecules based on disulfides and 1,2,4-triazole were synthesized, and the structures of the resulting compounds (7a–7g, 8a–8g and 9a–9g) were confirmed by their IR, 1H NMR, 13C NMR and HR-ESI-MS spectroscopic data. The in vitro antiproliferative activity of the tested compounds on human cancer cells A549, Hela, SMMC-7721, and normal cells L929 was determined by CCK-8 assay. The obtained data revealed that most of the tested compounds showed some degrees of antiproliferative activity, and some compounds displayed better effects than positive control 5-FU against various cancer cells. Especially, 3-phenyl-5-(n- butyldisulfanyl)-1,2,4-triazole（7c）exhibited highly effective antitumor activity against A549 cells with IC50 value of 3.55 μM. 3-(4-methoxyphenyl)-5-(n-hexyldisulfanyl) −1,2,4-triazole （9 g） was found to have the best inhibitory effect on Hela cells with IC50 value of 3.46 μM. 3-phenyl-5-(2-butyldisulfanyl)-1,2,4-triazole（7e）showed the greatest inhibitory activity on SMMC-7721 cells with IC50 value of 1.08 μM. In addition, all compounds exhibited weaker cytotoxic effects than 5-FU on L929 cells.

Unprecedented 4,9-Seco-Oplopanane and Seven Drimane Sesquiterpenoids from the Chinese Liverwort Lejeunea flava (Sw.) Nees.

An unprecedented 4,9-seco-oplopanane (1), two undescribed drimane epimers (2 and 3), and five known drimane sesquiterpenoids (4-8) were isolated from the Chinese liverwort Lejeunea flava (Sw.) Nees. The structures of the new sesquiterpenoids were determined using nuclear magnetic resonance spectroscopy, electronic circular dichroism calculations, and single-crystal X-ray diffraction measurements. The inhibitory capacity of the new compounds against nitric oxide production in lipopolysaccharide-induced RAW 264.7 murine macrophages, along with the cytotoxicity of the new compounds against A549 and HepG-2 human cancer cell lines, were discussed.

Synthesis and Biological Evaluation of Novel Allobetulon/Allobetulin-Nucleoside Conjugates as AntitumorAgents.

Allobetulin is structurally similar tobetulinic acid, inducing the apoptosis of cancer cells with low toxicity. However, both of them exhibited weak antiproliferation against several tumor cell lines. Therefore, the new series of allobetulon/allobetulin–nucleoside conjugates 9a–10i were designed and synthesized for potency improvement. Compounds 9b, 9e, 10a, and 10d showed promising antiproliferative activity toward six tested cell lines, compared to zidovudine, cisplatin, and oxaliplatin based on their antitumor activity results. Among them, compound 10d exhibited much more potent antiproliferative activity against SMMC-7721, HepG2, MNK-45, SW620, and A549 human cancer cell lines than cisplatin and oxaliplatin. In the preliminary study for the mechanism of action, compound 10d induced cell apoptosis and autophagy in SMMC cells, resulting in antiproliferation and G0/G1 cell cycle arrest by regulating protein expression levels of Bax, Bcl-2, and LC3. Consequently, the nucleoside-conjugated allobetulin (10d) evidenced that nucleoside substitution was a viable strategy to improve allobetulin/allobetulon’s antitumor activity based on our present study.

Two new cadinene-type sesquiterpene glycosides from Dendrobium findlayanum

Two new and one known cadinene-type sesquiterpene glycosides, findlayanosides A-B (1-2) and dendronobiloside D (3), were isolated from the stems of Dendrobium findlayanum. This is the first report that cadinene-type sesquiterpene glycosides were isolated from D. findlayanum. The structures of compounds 1 and 2 were elucidated by extensive spectroscopic analyses, and their absolute configurations were confirmed by electronic circular dichroism (ECD) calculations. The obtained compounds were evaluated for their cytotoxicity against HL-60, SMMC-7721, A-549 and MCF-7 human cancer cells, and no obvious cytotoxic activity was observed at the concentration of 25 μΜ.

Formation of Iridium(III) and Rhodium(III) Amine, Imine, and Amido Complexes Based on Pyridine-Amine Ligands: Structural Diversity Arising from Reaction Conditions, Substituent Variation, and Metal Centers.

Herein, we present the different coordination modes of half-sandwich iridium(III) and rhodium(III) complexes based on pyridine-amine ligands. The pyridyl-amine iridium(III) and rhodium(III) complexes, the corresponding oxidation pyridyl-imine products, and 16-electron pyridyl-amido complexes can be obtained through the change in reaction conditions (nitrogen/adventitious oxygen atmosphere, reaction time, and solvents) and structural variations in the metal and ligand. Overall, the reaction of pyridine-amine ligands with [(η5-C5(CH3)5)MCl2]2 (M = Ir or Rh) in the presence of adventitious oxygen afforded the oxidized pyridyl-imine complexes. The possible mechanism for the oxidation of iridium(III) and rhodium(III) amine complexes was confirmed by the detection of the byproduct hydrogen peroxide. Moreover, the formation of pyridyl-amine complexes was favored when nonpolar solvent CH2Cl2 was used instead of CH3OH. The rarely reported complex with [(η5-Cp*)IrCl3] anions can also be obtained without the addition of NH4PF6. The introduction of the sterically bulky i-Bu group on the bridge carbon of the ligand led to the formation of stable 16-electron pyridyl-amido complexes. The pyridyl-amine iridium(III) and rhodium(III) complexes were also synthesized under a N2 atmosphere, and no H2O2 was detected in the whole process. In particular, the aqueous solution stability and in vitro cytotoxicity toward A549 and HeLa human cancer cells of these complexes were also evaluated. No obvious selectivity was observed for cancer cells versus normal cells with these complexes. Notably, the represented complex 5a can promote an increase in the reactive oxygen species level and induce cell death via apoptosis.

Abstract 5480: Aristolochic acid as a scaffold for antitumor drug development

Abstract We have synthesized an analog of aristolochic acid (AA) with potent growth inhibitory activity in various human cancer cell lines and report here on mechanistic studies of this potential therapeutic. AA is a natural product and the main active principle of Aristolochia plants, a known source of antitumor agents. In 1964 due to nephrotoxicity, drug development efforts with AA were terminated following Phase I clinical trial in patients with terminal cancer of different origin. Structure activity studies of AA species allowed us to select a structural analog of AA (RJ-34) that lacks the determinants responsible for the renal toxicity and carcinogenicity of the parent compound. Building further on our experience with AA molecules, we developed a synthetic approach that affords efficient high-yield synthesis of RJ-34. Its structure and purity has been confirmed by high-performance liquid chromatography, liquid chromatography coupled with two-stage mass spectrometry and high resolution nucleic magnetic resonance. Sulforhodamine B assay revealed that RJ-34 has growth inhibitory activity in A549 and HCT-15 human cancer cell lines comparable to or stronger than that of paclitaxel or topotecan. At five nanomolar, RJ-34 inhibited DNA synthesis and cut the growth of A549 cells by 50%, leading to cell cycle arrest in G1/M and G2/S, with apparent apoptosis at concentrations greater than 200 nanomolar. Notably, protein synthesis in cultured cells, as evaluated by puromycin labelling, remained unaffected. RJ-34 was screened against the NCI-60 cell line panel - encompassing sixty human cancer cell lines from various tissues - providing clues to its mechanisms of action; namely, that RJ-34 acts through inhibition of DNA topoisomerases I and II and/or DNA intercalation. Follow-up studies using purified calf Topo I and human Topo II alpha and various plasmid substrates confirmed the role of RJ-34 as a DNA intercalator and human Topoisomerase II alpha poison. The pattern of activity of RJ-34 in the NCI-60 panel was distinct from that of AA and aristolactam - another related compound - suggesting that RJ-34 acts by mechanisms distinct from AA. In summary, RJ-34— a non-nephrotoxic analog of aristolochic acid— has a potent growth inhibitory activity in various human cancer cell lines with a mechanism of action different from the parent AA. Moving forward, pre-clinical pharmacokinetics, safety and efficacy studies are necessary to establish the potential of RJ-34 for development as an anticancer therapeutic. Citation Format: Keiji Hashimoto, Rajesh Chennamshetti, Radha Bonala, Francis Johnson, Arthur P. Grollman, Viktoriya S. Sidorenko. Aristolochic acid as a scaffold for antitumor drug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5480.

Bioactive prenylated phenolic compounds from the aerial parts of Glycyrrhiza uralensis

In this work, a bioassay-guided fractionation strategy was used to isolate 26 phenolic compounds from the ethyl acetate partition of an ethanol extract of the aerial parts of Glycyrrhiza uralensis Fisch. ex DC. Among them, 8 prenylated phenolic compounds (glycyuralins Q-X) were described for the first time. The two enantiomers of glycyuralin Q were purified and their absolute configurations were established by ECD spectral calculations. (1″R, 2″S)-glycyuralin Q and (1″S, 2″R)-glycyuralin Q showed significant inhibitory activities against SARS-CoV-2 virus proteases 3CLpro with IC50 values of 1.5 ± 1.0 and 4.0 ± 0.3 μM, and PLpro with IC50 values of 2.4 ± 0.2 and 1.9 ± 0.1 μM, respectively. Four compounds showed potent cytotoxic activities against A549, Huh-7, and HepG2 human cancer cells with IC50 values ranging from 0.5 to 2.5 μM.

A two-step strategy to synthesis new aminoguanidinium complexes: cytotoxic effect and perspectives

The progress of transition metal complexes having anticancer activity has greater influence in cancer therapy. With the anticipation of investigating the anticancer activity and property of the transition metal complexes, Ni(II), Zn(II), and Cd(II) metal complexes of 1-hydroxy-2-naphthoic acid (1H2NA)/2-hydroxy-1-naphthoic acid (2H1NA) with aminoguanidine of ratio 1:1:2 were synthesized and characterized by spectroscopic studies like IR, UV–Vis, Thermal analysis, powder XRD, molar conductivity measurements, antimicrobial, and anticancer studies. Simple salts of 1-hydroxy-2-naphthoic acid (1H2NA)/2-hydroxy-1-naphthoic acid (2H1NA) with aminoguanidine were also prepared in different ratios viz, 1:1 and 1:2. It is characterized by spectroscopic measurements IR, UV, TG-DTA, powder XRD, molar conductivity measurements, and cytotoxic effects were also studied. Nanometal oxides of zinc complexes were prepared and surface morphological studies were investigated. The functional groups were confirmed from IR spectroscopy data. Band gap energies of all the synthesized compounds were calculated from UV–Visible spectroscopy. Various decomposition steps and the thermal stability of the compounds were determined from thermal analysis. From the molar conductivity measurements, it is confirmed that the compounds are electrolytes. SEM and TEM images confirm the rod and hexagonal shape of the respective nanometal oxides. The complexes and nanometal oxides show significant activity against antimicrobials like Staphylococcus aureus, Escherichia coli, and Aspergillus fumigates. The results of present research show that, the synthesized ligands and metal complexes at lower concentration predominantly shows higher cytotoxic activity against cancer cellular lines like MCF-7 and A-549 (human breast cancer cells and human lung cancer cells, respectively). DFT computational studies were carried out using GAUSSIAN 09 W software to understand the bonding mode and chemical parameters of the complexes were calculated using frontier molecular orbital studies.

A New Sterol From the Polypore Fungus Ganoderma luteomarginatum and Its Cytotoxic Activities

A new sterol, ganolutol A (1), together with 4 known compounds 2 to 5, were isolated from the polypore fungus Ganoderma luteomarginatum collected in Myanmar. The chemical structures of the isolated compounds were determined based on extensive spectroscopic analyses in conjunction with comparisons with published data. Compounds 1 to 4 exhibited moderate cytotoxic activities against A549 (lung), MCF-7 (breast), and HeLa (cervical) human cancer cell lines, with IC50 values ranging from 10.1 to 86.6 μM.

Antitumor Activity and Physicochemical Properties of New Thiosemicarbazide Derivative and Its Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) Complexes.

A novel biologically active thiosemicarbazide derivative ligand L (N-[(phenylcarbamothioyl)amino]pyridine-3-carboxamide) and a series of its five metal(II) complexes, namely: [Co(L)Cl2], [Ni(L)Cl2(H2O)], [Cu(L)Cl2(H2O)], [Zn(L)Cl2] and [Cd(L)Cl2(H2O)] have been synthesized and thoroughly investigated. The physicochemical characterization of the newly obtained compounds has been performed using appropriate analytical techniques, such as 1H and l3C nuclear magnetic resonance (NMR), inductively coupled plasma (ICP), thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR) and magnetic measurements. In order to study the pharmacokinetic profile of the compounds, ADMET analysis was performed. The in vitro studies revealed that the synthesized compounds exhibit potent biological activity against A549 human cancer cell line.

Co-delivery nanosystem of Epigallocatechin Gallate and Rutin for anticancer and antibacterial activities

Although chemotherapy has successfully treated cancer to some extent, high doses, multiple drug resistance, undesirable toxic effects, and non-selective targeting are the major pitfalls. Nano drug materials have emerged as a promising method to improve the therapeutic benefit for extremely hydrophobic drugs, and nano-based combination therapy can potentially target these challenges. Here, an amphiphilic PEG-PCL diblock copolymer co-encapsulated with epigallocatechin-3-gallate and rutin nanorods within the range of 110 ± 15 nm and 26 ± 5.3 nm in length and width was developed as a combination therapy that synergistically combines features of anticancer and antibacterial activities. The drug release kinetics revealed that drug release from nanorods is due to anomalous diffusion with 77% of EGCG and 62% of rutin at lower pH 5.0 for a time period of 24 h. In vitro cytotoxicity assays against A549 human lung adenocarcinoma and HeLa cervical cancer cell lines showed that nanorods have a concentration-dependent synergistic effect in inducing intracellular reactive oxygen species (ROS) generation and cancer cell apoptosis by the up-regulation of caspase 9/3 activities. Confocal laser scanning microscopy further confirmed the potential internalization of nanorods into the cancer cells. Also, nanorods showed antibacterial effects against E. coli and S. aureus strains by cell membrane damage confirmed by time-killing kinetic studies and SEM analysis. Besides, hemolytic studies showed the biocompatibility of nanorods with human red blood cells. These findings hold promise for engineering multifunctional nanorods-based co-delivery systems targeting cancer and bacterial infections.