Cancer MCF-7 Cells Research Articles

Biological and computational assessment of new synthesized nicotinamides as potential immunomodulatory VEGFR-2 inhibitors

As an extension to our preceding studies on nicotinamide derivatives as anticancer agents, new nicotinamide-based candidates were designed and synthesized as VEGFR-2 inhibitors. The in vitro cytotoxic activity of the synthesized compounds was evaluated against three human cancer cell lines (MCF-7, HepG-2 and HCT-116). The IC50 values for compound 17 were 2.61± 0.01, 3.20 ± 0.02, and 2.46 ± 0.01 µM, respectively, compared to sorafenib (4.21±0.03, 3.40 ± 0.02, and 5.30 ± 0.04 µM) against MCF-7, HePG-2, and HCT-116. This indicated that compound 17 possess double strength relative to sorafenib against both MCF-7 and HCT-116. Compound 17 was the most promising VEGFR-2 inhibitor with IC50 value of 0.34 μM that was slightly better than that of sorafenib (0.38 μM). Further studies displayed the ability of compound 17 to arrest the growth of HCT-116 cells at the Pre-G1 and S phases. Additionally, compound 17 induced a significant increase in the total apoptosis rate of HCT-116 cells from 1.82 % to 26.69 %. Moreover, it showed high selectivity indices against HCT-116, HepG2, and MCF-7 cancer cells. Furthermore, compound 17 showed potent inhibitory activities on TNF-α and IL-6 and showed a notable rise in caspase-3 level. In addition, the potentiality of the designed derivatives to bind with and inhibit the VEGFR-2 enzyme was indicated by molecular docking assessments. MD simulation studies revealed the stability of compound 17 in the active site of VEGFR-2 for 100 ns. Based on the previous findings, compound 17 appears to be a promising apoptotic VEGFR-2 inhibitor and could potentially direct future efforts towards the development of novel anticancer medications.

Investigation of the effect of belinostat on MCF-7 breast cancer stem cells via the Wnt, Notch, and Hedgehog signaling pathway.

To evaluate belinostat's (PXD101) activity on MCF-7 breast cancer stem cells (CSCs) via Wnt, Notch, and Hedgehog. This research study was carried out at the Department of Medical Biology, Necmettin Erbakan University, Konya, Turkey, from June 2017 to July 2019. The effect of PXD101 on MCF-7 cell viability was determined by cell proliferation kit (XTT). Following belinostat treatment, CD44+/CD24- MCF-7 CSCs were isolated by FACS. Ribonucleic acid isolation and copy-deoxyribonucleic acid synthesis were carried out using HEK-293 cells, MCF-7 cells, and MCF-7 CSCs. Expression changes of metastasis-related genes, Wnt, Hedgehog, Notch, and stem cell markers were analysed by quantitative polymerase chain reaction. The IC50 in MCF-7 cancer cells was 5 μM for 48 hours. The FACS analysis indicated that 2% of the MCF-7 cancer cells were CSCs. Following belinostat treatment, the MCF-7 cell count decreased by 44%, and the MCF-7 CD44+/CD24- CSC count decreased by 66%. Belinostat treatment reduced the expression of metastasis, Wnt, Notch, Hedgehog, and stem cell marker genes. Belinostat has a potential effect on the differentiation and self-renewal of breast CSCs.

Biosynthesis of Gold Nanoparticles Using Aqueous Extract of Paramignya trimera Roots and Its Anticancer Activity

Developing environment-friendly processes for metal nanoparticle synthesis without using toxic chemical is very necessary to meet the demand for biological and medical applications. In this work, biosynthesis of gold nanoparticles (AuNPs) using aqueous extract of Paramignya trimera roots as the reducing and stability agents was carried out. The formation of gold nanoparticles was confirmed by the presence of an absorption peak at 550 nm using UV–Visible spectrophotometry. The size and morphology of gold nanoparticles was monitored by Field emission scanning electron microscopy (FE-SEM) and High resolution transmission electron microscopy (HR-TEM). Analysis of these particles showed the synthesized AuNPs were spherical in shape, with the particle size range of 10 nm–15 nm. The element gold and the crystalline nature of AuNPs were finalized using Energy dispersive X-ray (EDX) and X-ray diffraction (XRD) spectrometer, respectively. Fourier transform infrared (FTIR) spectroscopy revealed possible involvement of reductive groups on the surfaces of nanoparticles. The synthesized AuNPs are evaluated for its activity against MCF-7, HepG2, KB, LU-1 and MKN7 cancer cell lines with inhibition concentration 50% (IC50) of 2.01, 7.60, 3.89, 3.99 and 3.53 ppm respectively after 72 hours of treatment.

Synthetic Approaches to Novel Human Carbonic Anhydrase Isoform Inhibitors Based on Pyrrol-2-one Moiety.

New dihydro-pyrrol-2-one compounds, featuring dual sulfonamide groups, were synthesized through a one-pot, three-component approach utilizing trifluoroacetic acid as a catalyst. Computational analysis using density functional theory (DFT) and condensed Fukui function explored the structure-reactivity relationship. Evaluation against human carbonic anhydrase isoforms (hCA I, II, IX, XII) revealed potent inhibition. The widely expressed cytosolic hCA I was inhibited across a range of concentrations (KI 3.9-870.9 nM). hCA II, also cytosolic, exhibited good inhibition as well. Notably, all compounds effectively inhibited tumor-associated hCA IX (KI 1.9-211.2 nM) and hCA XII (low nanomolar). Biological assessments on MCF7 cancer cells highlighted the compounds' ability, in conjunction with doxorubicin, to significantly impact tumor cell viability. These findings underscore the potential therapeutic relevance of the synthesized compounds in cancer treatment.

Photoluminescent porous silicon nanowires as contrast agents for bioimaging

Porous silicon nanowires (pSi NWs) have attracted considerable interest due to their unique structural, optical properties and biocompatibility. The most common method for their top-down synthesis is metal-assisted chemical etching (MACE) of crystalline silicon (c-Si) wafers using silver nanoparticles as a catalyst. However, the replacement of silver with bioinert gold nanoparticles (Au NPs) markedly improves the efficiency of pSi NWs in biomedical applications. The present study demonstrates the fabrication of porous pSi NWs arrays using Au NPs as the catalyst in MACE of c-Si wafers with a resistivity of 1–5 mOhm·cm. Using scanning electron microscopy (SEM), the formation of arrays of porous nanowires with a diameter of 50 nm that consist of small silicon nanocrystals (nc-Si) and pores was observed. Raman spectroscopy analysis determined the size of nc-Si is about 4 nm. The pSi NWs exhibit effective photoluminescence (PL) with a peak in the red spectrum, which is attributed to the quantum confinement effect occurred in small 4 nm nc-Si. In addition, the pSi NWs exhibit low toxicity towards MCF-7 cancer cells, and their PL characteristics allow them to be used as contrast agents for bioimaging

Diving into paclitaxel: isolation and screening content from Taxus sumatrana at Singgalang Conservation Center, West Sumatra

The report features the first isolation of paclitaxel from wood of conservated Taxus sumatrana. The T. sumatrana is a nationally protected endemic plant that has been successfully cultivated outside its natural habitat at the Singgalang Conservation Centre in West Sumatra. The paclitaxel was utilised as a reference standard for evaluating its presence in different parts of T. sumatrana. This analysis exhibits that the acetone extract from T. sumatrana bark contained the highest paclitaxel concentration, measuring about 0.473 ± 0.031 ppm. The isolated paclitaxel demonstrated potent cytotoxic activity against A549, HeLa, and MCF7 cancer cells, by IC50 values of 3.26 ± 0.334, 2.85 ± 0.257, and 3.81 ± 0.013 μM, respectively. This outcome provides scientific support for conservation programs and campaigns for the community to engage in conservation efforts.

Investigations of new N1-substituted pyrazoles as anti-inflammatory and analgesic agents having COX inhibitory activity.

Background: The search is ongoing forideal anti-inflammatory and analgesic agents with promising potency and reasonable selectivity. Methods: New N1-substituted pyrazoles with or without anacetamide linkage were synthesized and evaluated for their anti-inflammatory and analgesic activities. COX inhibitory testing, molecular docking, molecular dynamics simulation and antiproliferative activity assessmentswere performed. Results: All compounds exhibited anti-inflammatory activity up to 90.40% inhibition. They also exhibitedgood analgesic activity with up to 100% protection. N1-benzensulfonamides 3d, 6c and 6h were preferentially selective agents towardCOX-2. Compound 3d showed good cytotoxicity against MCF-7 and HTC116 cancer cell lines. Molecular modeling studies predicted the binding pattern of the most active compounds. Molecular dynamics confirmed the docking results. All compounds showedremarkable pharmacokinetic properties.

New pyranopyrazole based derivatives: Design, synthesis, and biological evaluation as potential topoisomerase II inhibitors, apoptotic inducers, and antiproliferative agents

A new series of pyranopyrazole-based derivatives were designed and synthesized. The synthesized compounds were assessed for their cytotoxic efficacy against A549 human lung carcinoma and MCF-7 human breast carcinoma cell lines. Three compounds (1b, 4b, and 7b) exhibited 1.3- to 2.3-fold more antiproliferative activity than that of doxorubicin against the A549 cell line. In comparison to doxorubicin, compounds 1d and 3b were 4.1- and 1.04-fold, respectively more powerful against MCF-7 cancer cells. All the synthesized compounds were found to be more selective toward A549 cancer cells than the normal human fibroblast BJ cells. Of interest, compounds 1b and 7b exhibited promising cytotoxicity and SIs of 27.72 and 25.30, respectively, towards A549 cancer cells, higher than that of doxorubicin (SI 4.81). The most potent compounds 1b, 1d, 3b, 4b, and 7b were then subjected to in vitro Topo II inhibition assay. They showed IC50 values in the range of 2.07 to 8.86 µM. Of particular interest, compound 7b (IC50 = 2.07 µM), exhibited higher Topo II inhibitory activity than that of doxorubicin (IC50 = 2.56 µM). The significant Topo II inhibition of compound 7b was explained by molecular docking simulations into the Topo II active site. Compound 7b halted the cell cycle in the S phase in A549 cancer cells. It induced total apoptosis and necrosis of 20.73- and 4-fold, respectively, greater than the control. This evidence was supported by a 3.59-fold increase in the level of apoptotic caspase-9 and a remarkable elevation of the Bax/BCL-2 ratio. The physiochemical parameters of compound 7b were aligned with Lipinski’s rule of five.

Phototriggered Cytotoxicity of Ferrocene-Based Micelles - A Nonconventional Approach to Phototherapy.

We report the design, synthesis, and in vitro evaluation of stimuli-responsive nanoscale micelles that can be activated by light to induce a cytotoxic effect. Micelles were assembled from amphiphilic units made of a photoactivatable ferrocenyl linker, connected on one side to a lipophilic chain, and on the other side to a hydrophilic pegylated chain. In vitro experiments indicated that pristine micelles ("off" state) were nontoxic to MCF-7 cancer cells, even at high concentrations, but became potent upon photoactivation ("on" state). The illumination process led to the dissociation of the micelles and the concomitant release of iron species, triggering cytotoxicity.

Ruthenium-Cyclopentadienyl-Cycloparaphenylene Complexes: Sizable Multicharged Cations Exhibiting High DNA-Binding Affinity and Remarkable Cytotoxicity.

Two novel sizable multicharged cationic complexes, of the formulae [(η6--[12]CPP)[Ru(η5--Cp)]12]Χ12 and [(η6--[11]CPP)[Ru(η5--Cp)]11]Χ11, CPP = cycloparaphenylene, Cp = cyclopentadienyl, X = [PF6]-, (1), (3) and [Cl]-, (2), (4), were synthesized and characterized using NMR techniques, high-resolution mass spectrometry, and elemental analyses. Complexes (1) and (3) were stable in acetone and acetonitrile solutions over 48 h. In contrast, the water-soluble (2) and (4) begin to decompose in aqueous media after 1 h, due to the [Cl]- tendency for nucleophilic attack on ruthenium of the {Ru(η5--Cp)} units. Fluorescence quenching experiments conducted during the stability window of (2) with the d(5'-CGCGAATTCGCG-3')2-EtBr adducts revealed remarkably high values for Ksv = 1.185 × 104 ± 0.025 M-1 and Kb = 3.162 × 105 ± 0.001 M-1. Furthermore, the cytotoxic activity of (2) against A2780, A2780res, and MCF-7 cancer cell lines shows that it is highly cytotoxic with IC50 values in the range of 4.76 ± 1.85 to 16 ± 0.81 μΜ.

Biological Properties of Extracts Obtained from In Vitro Culture of Plectranthus scutellarioides in a Cell Model.

Plectranthus scutellarioides (L.) R.Br. is a medicinal plant that has long been used in traditional medicine to treat conditions such as abscesses, ulcers, and ear and eye infections. It is known to have a wide range of biological properties, such as antibacterial, antioxidant, antifungal, anti-inflammatory, anti-diabetic and anti-cancer effects. In this study, we established in vitro cultures from both the aerial parts and roots of Plectranthus scutellarioides. Subsequently, we compared the basic phytochemical profile of the obtained extracts and conducted a biological analysis to assess their potential for inducing apoptosis in breast (MCF-7) and lung (A549) cancer cells. Phytochemical analysis by HPLC-MS revealed the presence of compounds belonging to phenolic acids (ferulic, syringic, vanillic, rosmarinic, chlorogenic, caffeic, coumaric, dihydroxybenzoic acids), flavonoids (eriodyctiol and cirsimaritin), and terpenes such as 6,11,12,14,16-Pentahydroxy-3,17diacetyl-8,11,13-abietatrien-7-one, 6,11,12,14,16-Pentahydroxy-3,17-diacetyl5,8,11,13-abietatetraen-7-one, and 3,6,12-Trihydroxy-2-acetyl-8,12-abietadien7,11,14-trione. The results show that both extracts have a cytotoxic and genotoxic effect against MCF-7 and A549 cancer cells, with a different degree of sensitivity. It was also shown that both extracts can induce apoptosis by altering the expression of apoptotic genes (Bax, Bcl-2, TP53, Fas, and TNFSF10), reducing mitochondrial membrane potential, increasing ROS levels, and increasing DNA damage. In addition, it has been shown that the tested extracts can alter blood coagulation parameters. Our results indicate that extracts from in vitro cultures of Plectranthus scutellarioides aerial parts and roots have promising therapeutic application, but further research is needed to better understand the mechanisms of their action in the in vitro model.

Anti-proliferative activity of biosynthesized zinc oxide nanoparticles against breast cancer MCF-7 cells

Nanomaterials are a subject of immense interest within cancer research, primarily due to their promising role as potent anticancer agents, particularly in the context of targeted drug delivery. The present research work aims at exploring the antiproliferative potential of both undoped and metal doped Zinc oxide nanoparticles (ZnO NPs) synthesized using bio-assisted methods against MCF-7 breast cancer cell lines. Undoped and Cu and Ag metal doped ZnO NPs were synthesized using various bio-assisted methods and appropriately characterized using PXRD, FTIR, UV–vis spectroscopy, DLS and SEM. The NPs were subsequently diluted using ultrapure water to final concentrations ranging from 10 to 2.5 μg/ml. The antiproliferative efficiency of these NPs was assayed using WST-8 assay by measuring cell proliferation following exposure to various concentrations of these NPs over 24-h duration. The results of this study reveal that the undoped ZnO NPs synthesized using E officinalis fruit and P granatum peel aqueous extracts exhibit significant inhibitory impacts on MCF-7 cancer cells, particularly at higher concentrations. There was nearly a 45 % MCF-7 breast cancer cell line growth inhibition by both these NPs at the highest tested concentration of 10 μg/ml. Additionally, metal doped ZnO NPs demonstrated heightened inhibitory ability in comparison to undoped ones. Among Cu and Ag doped ZnO NPs, 3 M Ag doped ZnO NPs caused nearly 56 % MCF-7 breast cancer cell line growth inhibition at the highest tested concentration of 10 μg/ml.The authors noted that the adoption of novel bio-assisted synthesis methodologies showcases considerable potential in tailoring ZnO NPs properties to suit biomedical applications. Various forms of ZnO NPs used in the current study, underscores their potential as valuable tools in cancer treatment towards MCF-7 breast cancer cell lines, with a specific emphasis on the positive synergies realized when combining phytocompounds with ZnO NPs to enhance their antiproliferative effects.

Five undescribed aryltetralin lignans with cytotoxic activities from the fruits of Cleistanthus eberhardtii

Five undescribed lignans, cleiseberharnins A–D (1–4), cleiseberharside A (5) were isolated from the fruits of Cleistanthus eberhartii (Phyllanthaceae), together with six known aryltetralin lignans, cleistantoxin (6), picroburseranin (7), neocleistantoxin (8), 7-hydroxypicropolygamain (9), cleisindoside D (10), and cleisindoside A (11). Their structures and relative configurations were established by analysis of HRESIMS and NMR data, and quantum chemical calculations of JH,H coupling constants. The absolute configurations of 1–5 were determined by analysis of their experimental CD spectra and comparison with calculated electronic circular dichroism (ECD) spectra. All compounds (1−11) were evaluated for their cytotoxicity against KB, MCF-7, HepG-2, and Lu-1 human cancer cell lines. Among the tested compounds, compounds 6 and 7 showed strong activity against KB, MCF7, HepG2 and Lu-1 cell lines with IC50 values in the range of 0.02–0.62 μM. Compound 1 showed activity against three cancer cell lines KB, HepG2, and Lu-1 with IC50 values of 6.98, 7.61 and 11.75 μM, respectively. Compound 2 exhibited a selective inhibition with moderate cytotoxicity against Lu-1 with IC50 value of 15.30 μM. Compounds 4, 5 and 9 showed moderate activity against the three cancer cell lines with IC50 values in the range of 8.73–19.70 μM.

Clerodendrum chinense Stem Extract and Nanoparticles: Effects on Proliferation, Colony Formation, Apoptosis Induction, Cell Cycle Arrest, and Mitochondrial Membrane Potential in Human Breast Adenocarcinoma Breast Cancer Cells.

Breast cancer stands out as the most widespread form of cancer globally. In this study, the anticancer activities of Clerodendrum chinense (C. chinense) stem ethanolic extract were investigated. High-performance liquid chromatography (HPLC) analysis identified verbascoside and isoverbascoside as the major bioactive compounds in the C. chinense stem extract. Successfully developed nanoparticles exhibited favorable hydrodynamic diameter, polydispersity index, and surface charge, thus ensuring stability after four months of storage. The total phenolic content and total flavonoid contents in the nanoparticles were reported as 88.62% and 95.26%, respectively. The C. chinense stem extract demonstrated a dose-dependent inhibitory effect on MCF-7, HeLa, A549, and SKOV-3 cancer cell lines, with IC50 values of 109.2, 155.6, 206.9, and 423 µg/mL, respectively. C. chinense extract and NPs exhibited dose-dependent cytotoxicity and the highest selectivity index values against MCF-7 cells. A dose-dependent reduction in the colony formation of MCF-7 cells was observed following treatment with the extract and nanoparticles. The extract induced cytotoxicity in MCF-7 cells through apoptosis and necrosis. C. chinense stem extract and nanoparticles decreased mitochondrial membrane potential (MMP) and induced G0/G1 phase arrest in MCF-7 cells. In conclusion, use of C. chinense stem extract and nanoparticles may serve as a potential therapeutic approach for breast cancer, thus warranting further exploration.

Acylation of Oleanolic Acid Oximes Effectively Improves Cytotoxic Activity in In Vitro Studies.

(1) Background: The aim of the presented work was to obtain a set of oleanolic acid derivatives with a high level of anticancer activity and a low level of toxicity by applying an economic method. Three types of oleanolic acid derivatives were obtained: (i) derivatives of methyl oleanonate oxime, (ii) derivatives of methyl oleanonate oxime with an additional 11-oxo function, and (iii) derivatives of morpholide of oleanonic acid oxime. (2) Methods: The above oximes were acylated with aliphatic or aromatic carboxylic acid. The newly obtained compounds were subjected to ADMETox analysis and were also tested for cytotoxicity activity on the HeLa, KB, MCF-7, A-549, and HDF cell lines with the MTT assay. (3) Results: Among the tested acylated oximes of oleanolic acid, some derivatives, particularly those with two nitro groups attached to the aromatic ring, proved to be the most potent cytotoxic agents. These triterpene derivatives significantly inhibited the growth of the HeLa, KB, MCF-7, and A-549 cancer cell lines in micromolar concentrations. (4) Conclusions: The introduction of different moieties, particularly the 3,5-dinitro group, resulted in the synthesis of highly potent cytotoxic agents with favorable SI and ADMETox parameters.

C-30 analogues of betulinic acid as potent cytotoxic agents: design, synthesis, biological evaluation and in-silico studies

In an endeavour to improve the anti-cancer activity of betulinic acid (BA), a series of C-30 derivatives were envisaged and synthesized with a novel synthetic approach. All the derivatives were evaluated for cytotoxic activity by MTT assay against six different human cancer cell lines: prostate (PC3), lung (A549), human hepatocellular carcinoma (HepG2), human leukemia (Molt-4), pancreatic (Panc-1) and breast (MCF-7). The data revealed that compound 16 was observed most promising cytotoxic agent with IC50 values of 7.43 μM, 9.1 μM, and 9.64 μM against A549, MCF-7, and PC3 cancer cell lines respectively. A further mechanistic study confirmed compound 16 showed significant cell death by arresting the cell cycle in the G1 phase and inducing apoptosis in A549 cells. Communicated by Ramaswamy H. Sarma

The urolithin B nanomicellar delivery system as an efficient selective anticancer compound.

Urolithin B (UB), the antioxidant polyphenol has a protective impact on several organs against oxidative stress. However, its bioactivity is limited by its hydrophobic structure. In the current study, UB was encapsulated into a liposomal structure to improve its bioactivities anticancer, and antimicrobial potential. The UB nano-emulsions (UB-NE) were synthesized and characterized utilizing FESEM, DLS, FTIR, and Zeta-potential analysis. The UB-NMs' selective toxicity was studied by conducting an MTT assay on MCF-7, PANC, AGS, and ASPC1 cells. The AO/PI analysis verified the UB-NMs' cytotoxicity on ASPC1 cell lines and approved the MTT results. Finally, the antibacterial activity of the UB-NMs was studied on both gram-positive (B. subtilis, S. aureus) and gram-negative (E. Coli, P. aeruginosa) bacteria by conducting MIC and MBC analysis. The 68.15nm UB-NMs did not reduce the normal HDF cells' survival. However, they reduced the cancer cells' (PANC and AGS cell lines) survival at high treatment concentrations (> 250µg/mL) compared with normal HDF and cancer MCF-7 cells. Moreover, the IC50 doses of UB-NMs for the ASPC1 and PANC cancer cells were measured at 44.87, and 221.02µg/mL, respectively. The UB-NMs selectively exhibited apoptotic-mediated cytotoxicity on the human pancreatic tumor cell line (ASPC1) by down-regulating BCL2 and NFKB gene expression. Also, the BAX gene expression was up-regulated in the ASPC1-treated cells. Moreover, they exhibited significant anti-bactericidal activity against the E. coli (MIC = 50µg/mL, MBC = 150µg/mL), P. aeruginosa (MIC = 75µg/mL, MBC = 275µg/mL), B. subtilis (MIC = 125µg/mL, MBC = 450µg/mL), and S. aureus (MIC = 50µg/mL, MBC = 200µg/mL) strains. The significant selective cytotoxic impact of the UB-NMs on the human pancreatic tumor cell line makes it an applicable anti-pancreatic cancer compound. Moreover, the antibacterial activity of UB-NMs has the potential to decrease bacterial-mediated pancreatic cancer. However, several bacterial strains and further cancer cell lines are required to verify the UB-NMs' anticancer potential.

Actinoplanes pyxinae sp. nov., a new lichen-derived rare actinobacterium exhibiting antimicrobial and anticancer activity.

A novel lichen-derived actinobacterium, designated Pm04-4T, was isolated from Pyxine cocoes (Sw.) Nyl. lichen collected from Chaiyaphum, Thailand. A polyphasic approach was used to describe the taxonomic position of the strain. The strain had morphological and chemotaxonomic properties similar to members of the genus Actinoplanes. It produced sporangia on the substrate mycelia. Meso-diaminopimelic acid, galactose, glucose and mannose were detected in the whole-cell hydrolysate of the strain. The major menaquinone was MK-9(H4). The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannoside. The predominant cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0. Strain Pm04-4T showed the highest 16S rRNA gene sequence similarity to Actinoplanes akusuensis TRM 8003T (99.0 %). In the phylogenomic tree, strain Pm04-4T was positioned close to A. aksuensis TRM88003T, A. maris M416T, A. polyasparticus TRM66264T, A. hotanensis TRM88002T, A. abujensis DSM 45518T, A. bogorensis NBRC 110975T, A. brasiliensis DSM 43805T, A. lichenicola LDG1-01T and A. ovalisporus LDG1-06T. The average nucleotide identity and digital DNA-DNA hybridization values between strain Pm04-4T and its closely related neighbours were below the threshold values for describing new species. Moreover, the strain could be distinguished from its closely related type strains by phenotypic properties. Based on genotypic and phenotypic evidence, it can be concluded that strain Pm04-4T is a representative of a new Actinoplanes species for which the name Actinoplanes pyxinae sp. nov. is proposed. The type strain is Pm04-4T (=TBRC 16207T=NBRC 115836T). The type strain exhibited activity against Staphylococcus aureus ATCC 25923 as well as four yeast strains, namely Candida albicans TISTR 5554, Candida glabrata TISTR 5006, Candida krusei TISTR 5351 and Candida parapsilosis TISTR 5007. It also showed cytotoxicity against Caco-2, MNT-1 and MCF-7 cancer cells.

Development of new thieno[2,3-d]pyrimidines as dual EGFR and STAT3 inhibitors endowed with anticancer and pro-apoptotic activities

In part due to the resilience of cellular feedback pathways that develop therapeutic resistance to targeting the EGFR alone, using EGFR inhibitors alone was demonstrated to be unsuccessful in clinical trials. The over-activation of the signal transducer/activator of transcription 3 (STAT3) during the administration of an EGFR inhibitor is expected to play a substantial part in the failure and resistance of EGFR inhibitor treatment. Therein, we proposed a hypothesis that induced STAT3-mediated resistance to EGFR inhibition therapy could be addressed by a dual inhibition of EGFR and STAT3 method. To this end, we tried to discover new thieno[2,3-d]pyrimidine derivatives “5a-o”. Results from the screening on A549 and MCF7 cancer cell lines revealed that compounds 5j and 5k showed two-digit nanomolar with appropriate safety towards the WI-38 cell line. The best molecules, 5j and 5k, were subjected to γ-radiation, and their cytotoxic efficacy didn’t change after irradiation, demonstrating that not having to use it avoided its side effects. Compounds 5j and 5k demonstrated the highest inhibition when their potency was tested as dual inhibitors on EGFR 67 and 41 nM, respectively, and STAT3 5.52 and 3.34 nM, respectively, proved with in silico molecular docking and dynamic simulation. In light of the results presented above, the capacity of both powerful compounds to alter the cell cycle and initiate the apoptotic process in breast cancer MCF7 cells was investigated. Caspase-8, Bcl-2, Bax and Caspase-9 apoptotic indicators were studied.

Synthesis and characterization of quinoxaline-based rhenium(I) organometallic compounds: Biological and computational applications

Rhenium(I) organometallic compounds (C1-C6) with substituted quinoxaline Schiff base-based ligands (L1-L6) were synthesized and characterized using spectroscopic techniques such as 1HNMR , LC-MS, FT-IR spectroscopy, conductivity measurement, and elemental analysis. CT-DNA was tested under the impact of complexes using absorbance titration and viscosity measuring techniques to evaluate the binding capacities and manner. The compounds bind to the DNA by partial intercalation. The Kb values for all synthesized compounds are in the range of 0.44 to 1.72×105 M−1 in the absorption titration experiment. The evaluation of compounds binding to BSA was carried out using a fluorescence quenching study and the Ksv values were observed in the range of 0.93 to 1.67×104 M−1. The Ksv values for the fluorescence quenching-based DNA binding investigation were observed in the range of 0.75 to 1.87×104 M−1. The findings of the molecular docking investigations support the previously described point to an intercalation type of binding. The protein binding studies of all the synthesized compounds were examined using an absorption titration experiment, and the Kb values for all of the compounds range from 0.64 to 1.35×104 M−1. The structures of Re(I) complexes were optimized using DFT investigations. The antibacterial activity of organometallic compounds was tested against two Gram-positive and three Gram-negative pathogens, and the results showed that organometallic compounds outperform all ligands in this regard. The pharmacokinetic profile of each synthesized molecule was assessed as part of the ADME investigation using the online tools SwissADME and admetSAR. The MCF-7 cancer cell line was used to examine the anticancer effects of the compounds.