Mechanistic Insights into Bisphenol A-Mediated Male Infertility: Potential Role of Panax Ginseng Extract.

. The escalating prevalence of male infertility in the contemporary era across the globe can be largely attributed to environmental pollution, which is the common etiological factor due to the ubiquitous presence of the environmental contaminants. Bisphenol A is recognized as an endocrine-disrupting chemical that has adverse effects on both male and female reproductive systems. On the other hand, numerous studies have demonstrated that Panax ginseng possessed the potential to improve male infertility parameters; promote spermatogenesis, recover the quality and motility of sperm and enhance testicular functions as it acted as a natural androgen supplement. The objective of this review is to offer a summary of the findings obtained from the current research data on the insult of bisphenol A (BPA) on male infertility and its supposed mode of action, as well as shed light on the potent ameliorative role of Panax ginseng extract, with a special focus on the mechanism behind its action. This review delivers a clear understanding of BPA mechanism of action on male infertility and the presumed risks deriving from its exposure. Also, this review provides evidence for the functional role of Panax ginseng extract in restoring male fertility.

Synthesis, and anti-proliferative, Pim-1 kinase inhibitors and molecular docking of thiophenes derived from estrone.

Heterocyclization of steroids were reported to give biologically active products where ring D modification occured. Estrone (1) was used as a template to develop new heterocyclic compounds. Ring D modification of 1 through its reaction with cyanoacetylhydrazine and elemental sulfur gave the thiophene derivative 3. The latter compound reacted with acetophenone derivatives 4a-c to give the hydrazide-hydrazone derivatives 5a-c, respectively. In addition, compound 3 formed thiazole derivatives through its first reaction with phenylisothiocyanate to give the thiourea derivative 9 followed by the reaction of the later with α-halocarbonyl compounds. In the present work a series of novel estrone derivatives were designed, synthesized and evaluated for their in vitro biological activities against c-Met kinase, and six typical cancer cell lines (A549, H460, HT-29, MKN-45, U87MG and SMMC-7721). The most promising compounds 5b, 5c, 11a, 13c, 15b, 15c, 15d, 17a and 17b were further investigated against the five tyrosine kinases c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR. Compounds 5b, 15d, 17a and 17b were selected to examine their Pim-1 kinase inhibition activity where compounds 15d and 17b showed high activities. Molecular docking of some of the most potent compounds was demonstrated.

A free-standing, flexible PEDOT:PSS film and its nanocomposites with graphene nanoplatelets as electrodes for quasi-solid-state supercapacitors.

Research and development on all-solid-state, flexible supercapacitors is the prime concern of the scientific community these days due to their various advantages including their easy transportability, miniaturization, and compactness in different appliances. We report the novel configuration of all-solid symmetrical supercapacitors employing free-standing, flexible films of poly(3,4-ethylenedioxythiophene) poly(styrene sulfonate) (PEDOT:PSS) and its nanocomposite electrodes with graphene nanoplatelets (GNPs), separated by ionic liquid (IL) (1-ethyl 3-methylimidazolium trifluoromethanesulfonate (EMITf))-based gel polymer electrolyte (GPE) films. The free-standing and flexible form of PEDOT:PSS/GNP nanocomposite films have been prepared via simple mixing of the two counterparts. Scanning electron microscopy, x-ray diffraction, Raman analysis, and thermal and mechanical characterizations have been performed to ascertain the suitability of pristine and nanocomposite PEDOT:PSS films as potential supercapacitor electrodes. The GPE film, comprising of a solution of NH4CF3SO3 (NH4-triflate or NH4Tf) in IL, entrapped in poly(vinylidine fluoride-co-hexafluoropropylene) (PVdF-HFP), is a promising electrolyte due to its high ionic conductivity and sufficient electrochemical stability window. The supercapacitor with a PEDOT:PSS nanocomposite containing ∼3.8 wt.% of GNP has been found to give an optimum specific capacitance of ∼106 F g-1 (evaluated from electrochemical impedance spectroscopy), and specific energy and power of ∼6.95 Wh kg-1 and 2.58 kW kg-1, respectively (evaluated from galvanostatic charge-discharge). More importantly, the capacitors demonstrate stable performance for more than 2000 charge-discharge cycles, with only ∼10% initial fading in capacitance. Interestingly, the PEDOT:PSS/GNP nanocomposite-based solid-state supercapacitors with the IL-incorporated GPE have shown comparable (even better) performance than other reported PEDOT:PSS-based supercapacitors.

The Effect of Newly Synthesized Heterosteroids on miRNA34a, 98, and 214 Expression Levels in MCF-7 Breast Cancer Cells.

Hybrid anticancer drugs have emerged as great therapeutic options that can effectively overcome most obstacles facing conventional anticancer drugs. miRNAs are considered as class of non-coding RNAs that can negatively regulate protein coding gene expression. miRNA expression is commonly altered in cancer cells. The current work aimed to test the effect of new pro-apoptotic heterosteroids on some drug resistance related miRNAs expression levels (miRNA34a, 98, and 214) in MCF-7 breast cancer cells. After cell treatment with these compounds 4, 6, 7, 13, 18, 21, 22 and 24, miRNAs were extracted and subjected to reverse transcription and subsequent PCR amplification using Real Time-PCR technique. The expression levels of miR-34a, miR-98 and miR-214 were quantitatively determined. The study revealed that the expression levels of miR-34a, miR-98 and miR-214 were up-regulated upon treatment with tamoxifen, which was used as a positive control drug, as compared to control cells,. Strikingly, the levels of miR-34a, miR-98 and miR-214 expression were significantly down-regulated when treated with most of the new heterosteroids as compared to control cells. These results could indicate the promising effects of these new heterosteroids on reducing drug resistance as compared to tamoxifen drug. As well established, cells develop drug resistance to tamoxifen.

Some new nano-sized Fe(II), Cd(II) and Zn(II) Schiff base complexes as precursor for metal oxides: Sonochemical synthesis, characterization, DNA interaction, in vitro antimicrobial and anticancer activities.

The complexes of Fe(II), Cd(II) and Zn(II) with Schiff base derived from 2-amino-3-hydroxypyridine and 3-methoxysalicylaldehyde have been prepared. Melting points, decomposition temperatures, Elemental analyses, TGA, conductance measurements, infrared (IR) and UV-Visible spectrophotometric studies were utilized in characterizing the compounds. The UV-Visible spectrophotometric analysis revealed 1:1 (metal-ligand) stoichiometry for the three complexes. In addition to, the prepared complexes have been used as precursors for preparing their corresponding metal oxides nanoparticles via thermal decomposition. The structures of the nano-sized complexes and their metal oxides were characterized by X-ray powder diffraction and transmittance electron microscopy. Moreover, the prepared Schiff base ligand, its complexes and their corresponding nano-sized metal oxides have been screened in vitro for their antibacterial activity against three bacteria, gram-positive (Microccus luteus) and gram-negative (Escherichia coli, Serratia marcescence) and three strains of fungus. The metal chelates were shown to possess more antimicrobial activity than the free Schiff-base chelate and their nano-sized metal oxides have the highest activity. The binding behaviors of the complexes to calf thymus DNA have been investigated by absorption spectra, viscosity mensuration and gel electrophoresis. The DNA binding constants reveal that all these complexes interact with DNA through intercalative binding mode. Furthermore, the cytotoxic activity of the prepared Schiff base complexes on human colon carcinoma cells, (HCT-116 cell line) and hepatic cellular carcinoma cells, (HepG-2) showed potent cytotoxicity effect against growth of carcinoma cells compared to the clinically used Vinblastine standard.

New Approaches for the Synthesis, Cytotoxicity and Toxicity of Heterocyclic Compounds Derived from 2-Cyanomethylbenzo[c]imidazole.

The reaction of ethyl cyanoacetate with o-phenylenediamine gave the 2-cyanomethylbenzo[c]imidazole (1). The latter compound was used as the key starting material to synthesise biologically active heterocyclic derivatives. Thus, the reaction of 1 with cyclohexanone and either of benzaldehyde, 4-methoxybenzaldehyde or 4-chlorobenzaldehyde gave the annulated derivatives 2a-c, respectively. The antitumor evaluations of the newly synthesized products against the three cancer cell lines MCF-7 (breast adeno-carcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer) showed that compounds 2b, 6, 11b, 11c, 12b, 16a, 16b and 18a exhibited optimal cytotoxic effect against cancer cell lines, with IC50 values in the nM range. Bioactive compounds are often toxic to shrimp larvae. Thus, in order to monitor these chemicals in vivo lethality to shrimp larvae (Artemia salina), Brine-Shrimp Lethality Assay was used. Compounds 11b, 12b and 16b showed no toxicity against the tested organisms.

Uses of 3-(2-Bromoacetyl)-2H-chromen-2-one in the Synthesis of Heterocyclic Compounds Incorporating Coumarin: Synthesis, Characterization and Cytotoxicity.

In this work, 3-bromoacetylcoumarin was used as the key starting material for the synthesis of pyran, pyridine, thiophene, thiazole and pyrazole derivatives through its reaction with different reagents. The structures of the newly synthesized compounds were confirmed on the basis of their spectral data and elemental analyses. All of the synthesized compounds were screened for their in vitro anticancer activity against six human cancer cell lines, namely: human gastric cancer (NUGC), human colon cancer (DLD1), human liver cancer (HA22T and HEPG2), nasopharyngeal carcinoma (HONE1), human breast cancer (MCF) and normal fibroblast cells (WI38). The IC50 values (the sample concentration that produces 50% reduction in cell growth) in nanomolars (nM)) showed most of the compounds exhibited significant cytotoxic effect. Among these derivatives, compound 6d showed almost equipotent cytotoxic activity against NUGC (IC50 = 29 nM) compared to the standard CHS 828 (IC50 = 25 nM).

Anti-proliferative, Morphological and Molecular Docking Studies of New Thiophene Derivatives and their Strategy in Ionic Liquids Immobilized Reactions.

BACKGROUND: A number of research were conducted on the pyran and thiophene derivatives, which were attributed to have a wide range of biological activities, including anti-plasmodial, as well as acting as caspase, hepatitis C and cancer inhibitors. OBJECTIVE: The multicomponent reactions of the 5-acetyl-2-amino-4-(phenylamino)-thiophene-3-carbonitrile produced biologically active target molecules like pyran and their fused derivatives. Comparison between regular catalytic multi-component reactions and solvent-free ionic liquids immobilized multicomponent was studied. METHODS: The multicomponent reactions in this work were carried out not only under the reflux conditions using triethylamine as a catalyst but also in solvent-free ionic liquids immobilized magnetic nanoparticles (MNPs) catalysts. RESULTS: Through this work, thirty-one new compounds were synthesized and characterized and were evaluated toward the six cancer cell lines, namely A549, HT-29, MKN-45, U87MG, and SMMC-7721 and H460. The most active compounds were further screened toward seventeen cancer cell lines classified according to the disease. In addition, the effect of compound 11e on the A549 cell line was selected to make further morphological changes in the cell line. The Molecular docking studies of 11e and 11f were carried and promising results were obtained. CONCLUSION: The synthesis of heterocyclic compounds derived from thiophene derivatives has been receiving significant attention. After a detailed optimizing study, it has been found that the solvent-free ionic liquids immobilized multi-component syntheses afforded a high yield of compounds, opening a greener procedure for this synthetically relevant transformation. Many of the synthesized compounds can be considered anticancer agents, enhancing further studies.

New approaches for the synthesis of thiophene derivatives with anti-tumor activities.

The reaction of either cyclohexanone or cyclopentanone with cyanoacetylhydrazine and elemental sulfur gave the 2-aminocycloalkeno[b]thiophene derivatives 3a and 3b, respectively. The latter compounds reacted with either aromatic benzaldehydes or active methylene reagents to give the Schiff's bases 5a-d and the pyrazole derivatives 7a-d and 9a-d, respectively. On the other hand, the reaction of 3-oxo-N-p-tolylbutanamide (10) with either of malononitrile or ethyl cyanoacetate gave the thiophene derivatives 13a and 13b, respectively. Compounds 13a,b were subjected to a series of heterocyclization reactions to give heterocyclic derivatives. Their cytotoxicity against the three human tumor cells lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) together against the normal human cell line namely the normal fibroblast cells WI 38 were measured.

New Approaches for the Synthesis N-alkylated Benzo[b]thiophene Derivatives together with their Antiproliferative and Molecular Docking Studies.

BACKGROUND: 2-Amino thiophene derivatives are important compounds not only for their uses in many heterocyclic reactions but also due to their wide range of pharmaceutical and biological activities. OBJECTIVE: The aim of this work was to explore a number of new heterocyclic derivatives, studying their inhibitions toward cancer cell lines and studying their structure activity relation ship. METHODS: Alkylation of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile was achieved through its reaction with chloroacetone and 2-bromo-1-(4-aryl)ethanone derivatives to give compounds 3 and 11a-c. The produced compoumds were subjected to further heterocylization reactions and cytotoxic evaluation against the three cancer cell lines MCF-7, NCI-H460 and SF-268, together with the normal cell line WI 38. Further evaluations were obtained through studying their inhibitions against cancer cell lines classified according to the disease. Anticancer screening against hepatocellular carcinoma HepG2 and cervical carcinoma HeLa cell lines for all compounds together with the molecular docking of 12c, 12d, 12e and 12f were studied. RESULTS: Anti-proliferative evaluations and inhibitions for all of the synthesized compounds showed that many compounds exhibited high inhibitions. CONCLUSION: Toward the three cancer cell lines, compounds 3, 5a, 7a, 9a, 9b, 11b, 12b, 12d, 12e, 12f, 14c, 14e, 14f, 15e, 15f, 16e, 16f, 17c, 18b, 22a and 22c were the most cytotoxic compounds. The high activities of some compounds were attributed to the presence of the electronegative CN and or Cl groups within the molecule. Most of the tested compounds exhibited inhibitions higher than the reference doxorubicin toward hepatocellular carcinoma HepG2 and cervical carcinoma HeLa cell lines. The score of binding energy of compounds 12c, 12d, 12e and 12f was close to the reference Foretinib which appeared through the molecular docking results of such compounds.

Synthesis, Molecular Docking, c-Met Inhibitions of 2,2,2-Trichloroethylidene- cyclohexane-1, 3-dione Derivatives Together with their Application as Target SARS-CoV-2 main Protease (Mpro) and as Potential anti-COVID-19.

BACKGROUND: The lack of anti-COVID-19 treatment to date warrants urgent research into potential therapeutic targets. Virtual drug screening techniques enable the identification of novel compounds that target the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Main Protease (Mpro). OBJECTIVE: The binding of the halogenated compounds to Mpro may inhibit the replication and transcription of SARS-CoV-2 and, ultimately, stop the viral life cycle. In times of dire need for anti- COVID-19 treatment, this study lays the groundwork for further experimental research to investigate these compounds' efficacy and potential medical uses to treat COVID-19. METHODS: New heterocyclic compounds were synthesized through the first reaction of cyclohexane- 1, 3-dione (1a) or dimedone (1b) with trichloroacetonitrile (2) to give the 2,2,2-trichloroethylidene) cyclohexane-1,3-dione derivatives 3a and 3b, respectively. The latter compounds underwent a series of heterocyclization reactions to produce biologically active compounds. RESULTS: Novel compounds, including fused thiophene, pyrimidine and pyran derivatives, were synthesized and tested against human RNA N7-MTase (hRNMT) and selected viral N7-MTases such as SARS-CoV nsp14 and Vaccinia D1-D12 complex to evaluate their specificity and their molecular modeling was also studied in the aim of producing anti-COVID-19 target molecules. CONCLUSION: The results showed that compounds 10a, 10b, 10c, 10e, 10f, 10g and 10h showed high % inhibitions against SARs-Covnsp 14. Whereas compounds 5a, 7a, 8b, 10a, 10b, 10c and 10i showed high inhibitions against hRNMT. This study explored the binding affinity of twenty-two halogenated compounds to the SARS-CoV-2 MPro and discovered fifteen compounds with higher binding affinity than Nelfinavir, of which three showed remarkable results. c-Met kinase inhibitions of 10a, 10f, 10g and 10h showed that all compounds exhibited higher inhibitions than the reference Foretinib.

Uses of cyanoacetylhydrazine in heterocyclic synthesis: novel synthesis of pyrazole derivatives with anti-tumor activities.

The reaction of cyanoacetylhydrazine with chloroacetyl chloride gave N'-(2-chloroacetyl)-2-cyanoacetohydrazide. The latter underwent cyclization to afford 1-(5 amino-3-hydroxy-1H-pyrazol-1-yl)-2-chloroethanone, which underwent nucleophilic substitution to give 3-(5-amino-3-hydroxy-1H-pyrazol-1-yl)-3-oxopropanenitrile. The latter two compounds were used as key synthons to synthesize new thiophene, pyran, thiazole and some fused heterocyclic derivatives. The antitumor activity of the newly synthesized compounds was evaluated against three human tumor cells lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) and some of these compounds were found to exhibit much higher inhibitory effects towards the three tumor cell lines than the Gram positive control doxorubicin.

Anxiety and depression among traumatic spinal cord injured patients.

OBJECTIVE: To investigate the relation between gender, sociodemographic factors, pain, smoking, and the level of anxiety and depressive symptoms after traumatic spinal cord injury (TSCI) in a Saudi sample. METHODS: We conducted a cross-sectional study from November 2009 to April 2011, in 102 (age range 17-70 years; 84 males, 18 females) TSCI patients admitted to the Spinal Cord Injury Unit, Sultan Bin Abdulaziz Humanitarian City, Riyadh, Saudi Arabia. We used the Hospital Anxiety and Depression Scale (HADS) to measure the level of anxiety and depression of the study population. The demographic variables were recorded. RESULTS: Compared to male TSCI patients, the level of anxiety (p=0.0001), depression (p=0.0045), and total HADS (p=0.0002) scores were significantly higher in females. The correlation between level of education and anxiety and depression showed that patients with a university education had higher anxiety (p=0.0115), depression (p=0.0437), and total HADS (p=0.0272) than patients with a lower education level. The TSCI patients with pain reported more anxiety and depression than patients who did not have pain. Compared to non-smokers, the smokers showed marked but insignificant higher levels of anxiety and depression. CONCLUSION: Women with TSCI are at a significantly higher risk of having anxiety and depressive symptoms. Level of university education was modestly correlated with higher level anxiety and depression in this population.

Anti-proliferative, c-Met Inhibitions, and PAINS Evaluations of New Thiophene, Thiazole, Coumarin, Pyran, and Pyridine Derivatives.

BACKGROUND: 1,3-Diones are versatile reagents used for many heterocyclic transformations. Among such groups of compounds, cyclohexane-1,3-dione is widely used in organic synthesis to produce biologically active compounds. OBJECTIVE: In this work, target molecules were synthesized from tetrahydrobenzo[b]thiophen-3- carboxamide derivative with different substituents, and their structure-activity relationships were discussed in detail. METHODS: Cyclohexane-1,3-dione underwent different multi-component reactions to produce fused thiophene, thiazole, coumarin, pyran, and pyridine derivatives. The anti-proliferative activity of the newly synthesized compounds toward the six cancer cell lines, namely A549, H460, HT-29, MKN-45, U87MG, and SMMC-7721 was studied. In addition, inhibitions of the most active compounds toward cancer cell lines classified according to the disease were also studied. Furthermore, Pan Assay Interference compounds (PAINS) of the selected compounds were analyzed, along with the c- Met inhibitions. RESULTS: Anti-proliferative evaluations were performed for all of the synthesized compounds, in which the varieties of substituents through the aryl ring and the heterocyclic ring afforded compounds with high activities. Inhibition activity against the cancer cell lines classified according to the disease, c-Met, and PAINS of the synthesized compounds were measured. CONCLUSION: Compounds 3, 13a, 13b, 14a, 16f, 17a, 28, 30a, and 31were the most cytotoxic compounds toward the six cancer cell lines. Inhibition toward cancer cell lines classified according to the disease showed that, in most cases, the presence of the electronegative CN and or Cl groups within the molecule was responsible for its high activity.

New Approaches for the Synthesis of 2,3,5,6-Tetrahydrobenzo[d]thiazole Derivatives and their Anti-Proliferative, c-Met Enzymatic Activity and Tyrosine Kinases Inhibitions.

BACKGROUND: Due to their biological applications, many tetrahydrobenzo[d]thiazole derivatives were considered the most important class of heterocyclic compounds. There are many drugs known in the market containing the thiazole moiety responsible for the high drug activity. OBJECTIVE: This work aimed to produce novel heterocyclic compounds such as pyrazole, isoxazole, thiophene, chromeno[ 7,8-d]thiazole, and thiazolo[4,5-h]quinoline derivatives. The newly synthesized heterocyclic compounds were evaluated against anticancer cell lines followed by c-Met enzymatic activity and tyrosine kinases inhibition for the most active compounds. METHODS: In this work, the 3-phenyl-2-thioxo-2,3,5,6-tetrahydrobenzo[d]thiazol-7(4H)-one (3) was synthesized through the reaction of cyclohexane-1,3-dione with phenyl isothiocyanate and elemental sulfur. Compound 3 showed interesting activity toward some chemical reagents producing new heterocyclic compounds that can not be obtained another way. The newly synthesized compounds were evaluated towards the six cancer cell lines. The most active compounds were selected and tested toward the c-Met enzyme by taking foretinib as the positive control. Also, the inhibitions toward the PC-3 cell line using the reference SGI-1776 were measured. Finally, the inhibitions towards the five tyrosine kinases were also tested. RESULTS: The synthesized quinoline and chromene derivatives were evaluated toward the c-Met enzyme using foretinib as the positive control. The obtained results showed that twelve compounds exhibited IC50 values less than 1.30 nM. On the other hand, sixteen compounds showed higher inhibitions than the reference SGI-1776 (IC50 4.86 nM) toward the PC-3 cell line. CONCLUSION: Novel, heterocyclic compounds were synthesized with a high impact on biological activities. All synthesized compounds were screened for their anti-proliferative effect, and most of them revealed high potent effects. In addition, the c-Met and prostate cancer cell line PC-3 inhibitions for the most active compounds showed that these compounds exhibited high inhibitions. Anti-proliferative activity of selected compounds toward cancer cell lines classified according to the disease showed that most compounds exhibited high inhibitions.

Cellulose-based activated carbon/layered double hydroxide for efficient removal of Clarithromycin residues and efficient role in the treatment of stomach ulcers and acidity problems.

The terrible rise of antibiotic residues which possesses a serious threat to the ecological and aquatic environments. So, the development of highly cost-effective, highly operation-convenient and recyclable adsorbents was a must. In our study, we utilized the ternary layered double hydroxide (CoZnAl LDH) as an efficient adsorbent and nano-carrier for Clarithromycin (CLA) residues for their biodegradability and biocompatibility. Also, we enhanced the removal efficiency of the synthesized ternary LDH using cellulose-based activated carbon which was obtained using the hydrothermal carbonization method followed by chemical activation via static air converting the cellulose derivative (hydroxy ethyl cellulose HEC) into highly porous activated carbon that played an important role in the adsorption process. Full characterization of the synthesized activated carbon (AC) and the adsorbents before and after the adsorption processes were carried out using different techniques. The differences between the two adsorbents were investigated in a comparative study in terms of factors affecting the adsorption process like pH, the dose of adsorbent, time, and temperature. The adsorption isotherm was investigated at pH 10 with high regression coefficient (R2) of 0.99 showing maximum adsorption capacity (qmax) of 61.5 mg/g for (CLA) using LDH as adsorbent, whereas, the investigation using the modified LDH (LDH-AC) with high regression coefficient (R2) of 0.99 shows maximum adsorption capacity (qmax) of 495 mg/g for (CLA). Kinetic studies were estimated. The thermodynamic parameters such as ΔS°, ΔG° and ΔH° were estimated showing that the adsorption processes undergo exothermic and spontaneous routes. The safety and cytotoxicity of the modified, synthesized LDH (LDH-AC) were investigated besides the investigation of the gastroprotective efficacy against generated stomach ulcers. (LDH-AC) showed significant reduction for the generated ulcer in addition to the enhancement of the gastro protective efficacy revealing the safe use of LDH-AC/CLA for biological purposes like ulcer reduction and the enhancement of the ulcer inhibition.

Synthesis, structural elucidation, DFT calculation, biological studies and DNA interaction of some aryl hydrazone Cr3+, Fe3+, and Cu2+ chelates.

The current research focuses on the treatment of Cr(III), Fe(III) and Cu(II) metal ions with aryl hydrazone ligand named (E)-4-(((diphenylmethylene)hydrazono)methyl)benzene-1,3-diol (DPHB) to afford four novel solid complexes with high yields. Different characterization approaches, including infrared, UV-visible, and NMR spectroscopies, elemental analyses, and thermal gravimetric analysis (TGA), revealed that all mononuclear crystalline metal chelates with good thermal stability had a six-coordination with octahedral geometry. Density Functional Theory (DFT) computations were used and provided a reasonable explanation for these metal chelates' electrical and structural features. Furthermore, investigations of electronic absorption spectroscopy, hydrodynamics, and electrophoresis demonstrated that these new compounds interact with calf thymus deoxyribonucleic acid (CT-DNA) in a variety of ways. As a result, the Kb and ∆Gb≠ values of such interactions were in the following order: DPHBCu > DPHBCr > DPHBFe complex. Additionally, the novel metal chelates have been studied anti-bathogenically and found to be significantly effective compared to the comparable DPHB hydrazone ligand. The anti-proliferative activities of the investigated compounds were also evaluated against different lines of cancer cells and exhibited significant cytotoxic activity. In addition, observations of antioxidant activity suggest that antioxidant activity relative to ordinary ascorbic acid was demonstrated in the molecule.

Molecular Mechanisms Underlying the Anti-Breast Cancer Stem Cell Activity of Pterocladia capillacea and Corallina officinalis Polysaccharides.

OBJECTIVE: This study aimed to appraise the activity of Pterocladia capillacea and Corallina officinalis polysaccharides against Breast Cancer Stem Cells (BCSCs). P. capillacea and C. officinalis polysaccharides were characterized to be sulfated polysaccharide-protein complexes. METHODS: Cytotoxicity of the polysaccharides against MDA-MB-231 and MCF-7 cell lines along with their impact on CD44+/CD24- and aldehyde dehydrogenase 1(ALDH1) positive BCSC population were determined. Their effect on gene expression of CSC markers, Wnt/ß-catenin and Notch signaling pathways was evaluated. RESULTS: P. capillacea and C. officinalis polysaccharides inhibited the growth of breast cancer cells and reduced BCSC subpopulation. P. capillacea polysaccharides significantly down-regulated OCT4, SOX2, ALDH1A3 and vimentin in MDA-MB-231 as well as in MCF-7 cells except for vimentin that was up-regulated in MCF-7 cells. C. officinalis polysaccharides exhibited similar effects except for OCT4 that was up-regulated in MDA-MB-231 cells. Significant suppression of Cyclin D1 gene expression was noted in MDA-MB-231 and MCF-7 cells treated with P. capillacea or C. officinalis polysaccharides. ß-catenin and c-Myc genes were significantly down-regulated in MDA-MB-231 cells treated with C. officinalis and P. capillacea polysaccharides, respectively, while being up-regulated in MCF-7 cells treated with either of them. Additionally, P. capillacea and C. officinalis polysaccharides significantly down-regulated Hes1 gene in MCF-7 cells despite increasing Notch1 gene expression level. However, significant down-regulation of Notch1 gene was observed in MDA-MB-231 cells treated with P. capillacea polysaccharides. CONCLUSION: Collectively, this study provides evidence for the effectiveness of P. capillacea and C. officinalis polysaccharides in targeting BCSCs through interfering with substantial signaling pathways contributing to their functionality.

Waste Valorization of a Recycled ZnCoFe Mixed Metal Oxide/Ceftriaxone Waste Layered Nanoadsorbent for Further Dye Removal.

Waste valorization of spent wastewater nanoadsorbents is a promising technique to support the circular economy strategies. The terrible rise of heavy metal pollution in the environment is considered a serious threat to the terrestrial and aquatic environment. This led to the necessity of developing cost-effective, operation-convenient, and recyclable adsorbents. ZnCoFe mixed metal oxide (MMO) was synthesized using co-precipitation. The sample was characterized using X-ray powder diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. Factors affecting the adsorption process such as pH, the dose of adsorbent, and time were investigated. ZnCoFe MMO showed the maximum adsorption capacity of 118.45 mg/g for ceftriaxone sodium. The spent MMO was recycled as an adsorbent for malachite green (MG) removal. Interestingly, the spent adsorbent showed 94% removal percent for MG as compared to the fresh MMO (90%). The kinetic investigation of the adsorption process was performed and discussed. In addition, ZnCoFe MMO was tested as an antimicrobial agent. The proposed approach opens up a new avenue for recycling wastes after adsorption into value-added materials for utilization in adsorbent production with excellent performance as antimicrobial agents.

Anti-tumor and anti-leishmanial evaluations of 1,3,4-oxadiazine, pyran derivatives derived from cross-coupling reactions of ß-bromo-6H-1,3,4-oxadiazine derivatives.

Cyanoacetylhydrazine reacted with the ω-bromoacetophenones 2a,b to give hydrazide-hydrazone derivatives 3a,b. The latter products were cyclized to the 1,3,4-oxadiazine derivatives 4a,b. Bromination of the latter products gave the 6-bromo-6H-1,3,4-oxadiazine derivatives 5a,b which underwent a series of cross-coupling reactions. The antitumor evaluation of the newly synthesized products against the three cancer cells namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) showed that some of them have high inhibitory effect towards three cell lines which is higher than the standard. Moreover, the anti-leishmanial activity of the newly synthesized product was tested on Leishmania donovani amastigotes showed that some compounds have high activity.