Mammary Gland Breast Cancer Research Articles

Synthesis, Characterization, and Molecular Docking of Novel Isatin-thiosemicarbazone containing 1,2,3-triazole Derivatives as Potential Anti-cancer Agents

Abstract: To improve the activity of isatin-1,2,3-triazole hybrids as anticancer agents, new derivatives of isatin- thiosemicarbazone-1,2,3-triazoles 9-16 were designed and synthesized via the condensation of isatin-1,2,3- triazole hybrids 1-8 with thiosemicarbazide. Spectral and elemental analysis confirmed the structure of the prepared derivatives 9-16. Also, as anticancer agents, the latter derivatives were screened against three human cancerous cell lines: human lung fibroblast (WI38), colorectal carcinoma colon cancer (HCT-116), and mammary gland breast cancer (MCF-7). Doxorubicin, a standard control, was used to compare viable cell percentages and IC50 values. In general, derivatives 12 and 16 revealed a higher potency against the three human cancerous cell lines. Finally, the molecular descriptors of compounds 12 and 16 were correlated with their observed cytotoxicity. result: In general, derivatives 12 and 16 revealed a higher potency against the three human cancerous cell lines.

Microwave synthesis, density functional theory study and antiproliferative activity of the novel spiropyrazole derivatives

Different spiro-pyrazole-oxy-indoline substituted compounds I-IV have been synthesized. In Jaguar, Hybrid DFT using Becke’s three-parameter transfer possibility also,Lee-Yang-Parr correlated practical (B3LYP) viewwith a 6-31 G** basis set were utilized to improve the geometrical characteristics of the hit molecules and reference compound. The MTT test exhibited whether the prepared substance has an inhibitory impact on cell development or not. This was successfully represented that in hepatocellular carcinoma (HEPG-2), colorectal carcinoma (HCT-116), and mammary gland breast cancer cell lines (MCF-7) colorimetric test, the mitochondrial succinate dehydrogenase in live cells transform yellow tetrazolium bromide (MTT) to a purple formazan product. Compound IV was found to be a better cytotoxic action against to the HEPG-2 hepatocellular carcinoma cell line, and it has been seen a strong activity against the colorectal carcinoma cell lines HCT-116 and MCF-7 mammary gland breast cancer cell lines. While the other three compounds I, II, and III showed a moderate cytotoxic action to high action against the same cell lines.

Synthesis, structural characterization, density functional theory, anticancer, and antimicrobic studies of Ni2+ and Cu2+ complexes encompassing tridentate ONS‐donor azo‐thiosemicarbazone

This study focuses on the synthesis of azo‐thiosemicarbazone ligand, which is designed by reacting 2‐hydroxy‐5‐(phenyldiazenyl)benzaldehyde with hydrazine carbothioamide. Hence, this ligand was exploited for chelation with nickel and cupric salts in (1 M:1 L) molar ratio. These synthetics were structurally investigated using a variety of physical, analytical, and spectroscopic (1D/2D‐NMR, UV–Vis, FT‐IR, and E‐mass) tools as well as theoretically. The finding demonstrated that the resulting azo‐thiosemicarbazone (H4Azo‐TSC) bonded with the nickel and cupric ions as mono/di‐basic tridentate chelators, binding them via deprotonated phenolic oxygen, imino nitrogen, and thionic/thiol sulfur atoms adopting square planar geometry. The theoretical investigation was examined by DFT/B3LYP/LanL2dZ, including energetic parameters, HOMO‐LUMO energy gap, dipole moment, and geometrical optimization, which were applied to support the complexes' geometrical structure. The in vitro microbicidal activities of the azo‐thiosemicarbazone, compared with its Ni2+ and Cu2+ complexes, display superior activity over the metal complexes against different bacterial and fungal species. The anticancer efficacy of the synthetics was tested against human lung fibroblast (WI38) and mammary gland breast cancer (MCF‐7) compared with Doxorubicin as a standard drug. The cytotoxic efficiency of metallic complexes exceeded that of un‐chelated azo‐thiosemicarbazone. The most effective complex is Ni2+ complex with IC50 equal to 11.75 and 14.05 μg/ml, respectively. It has been demonstrated that Ni2+ and Cu2+ complexes are more biocompatible than free azo‐thiosemicarbazone; this finding may be related to the chelation process.

Design, synthesis, and molecular docking of novel 1,3, 4-triaryl pyrazole derivatives bearing methylsulfonyl moiety with anticancer activity through dual targeting CDK2 and COX-2 enzymes

Novel 3-(4-methylsulfonylphenyl) pyrazole derivatives with different substitutions at position four were designed, synthesized, characterized by spectroscopic techniques, and investigated as potential anticancer agents via inhibition of cyclin-dependent kinase 2 and cyclooxygenase-2 enzymes. All the synthesized compounds were screened against three cancer cell line panels, hepatocellular carcinoma (HepG-2), mammary gland breast cancer (MCF-7), and colorectal carcinoma (HCT-116), to determine their antiproliferative properties by MTT assay. Compounds 5a, 6a, 6c, and 10c exhibited a considerable antiproliferative effect on HepG-2 cell line with IC50 value of 2.88 to 8.57 µM, on HCT-116 cell line with IC50 value of 6.34 to 17.84 µM, and on MCF-7 cell line with IC50 value of 1.75 to 9.58 µM. Compounds 5a, 6a, 6c, and 10c had weak toxicity towards normal HEK-293T, especially 10c displayed the highest IC50 with a value of 101.21 μM against normal cells. Furthermore, mechanistic studies for the antiproliferative activity were performed on the most active compounds 5a, 6a, 6c, and 10c. Compound 6c exhibited significant inhibitory activity against CDK2 enzyme with IC50 value of 0.614 µM compared to R-roscovitine (IC50 = 0.533 µM) as a reference drug. Additionally, compounds 5a, 6a, 6c, and 10c have significant potency and selectivity for the COX-2 enzyme (IC50 = 0.058 – 0.089 µM) over COX-1 enzyme (IC50 = 9.7 – 11.6 µM) compared to celecoxib and indomethacin. Accordingly, compounds 5a and 6c showed potent COX-2 inhibitory activity with IC50 values of 0.058 and 0.075 µM with a selectivity index of 198.27 and 154.66, respectively, in comparison to celecoxib and indomethacin with COX-2 IC50 value of 0.046 and 0.079 µM and a selectivity index of 315.21 and 1.25. compound 6c, with the potent CDK2 and COX-2 inhibitory activity, demonstrated apoptotic activity on HepG-2 cancer cells by inducing a strong G1 phase cell cycle arrest. Also, compound 6c significantly elevated the Bax/Bcl-2 ratio by 14.54 folds compared to the untreated control, which is clearly correlated with its sensitivity to apoptosis. Molecular docking and dynamics simulations were conducted to illustrate the binding modes inside the active sites. Finally, the hit compound 6c was discovered to have antiproliferative activity against HepG-2, MCF-7, and HCT-116 cancer cell lines by inhibiting CDK2 and COX-2 enzymes as proposal mechanisms.

Activated cyanoacetamide in heterocyclic synthesis: Design, synthesis, antitumor activity and docking study of some new pyrimidine derivatives

The precursor cyanoacetamide derivatives (6) were achieved by the reaction of pyrimidine derivative 5 with cyanoacetic acid catalyzed by acetic anhydride. The reaction of cyanoacetamide derivative 6 with different reagents afforded many heterocyclic systems such as thioacetic acid (9), dithiolane derivatives (11) and (12), 1,8-naphthyridine (14), quinoline derivatives (17) and (18), pyridine derivatives 20, 22, 24, 26, and 27, pyridazine (30), pyranopyrimidine (32), and pyrazolopyrimidine (34). All the newly synthesized compounds were characterized with spectroscopic analyses. Compounds were tested for their anticancer activity against three human cancer cell lines: hepatocellular carcinoma (HepG-2), colon cancer (HCT-116), and mammary gland breast cancer (MCF-7). The studied compound's cytotoxic activity ranged from very strong to very weak. The most active compounds were 9, 10, 11, 27, and 34. The binding disposition of the docked compounds, in particular 9, 10, 11, 27, and 34, towards the binding site of AKT complexed with co-crystallized ligand was investigated using molecular docking (PDB = 4EJN).

Promising Cytotoxic butenolides from the Soybean endophytic fungus Aspergillus terreus: a combined molecular docking and in-vitro studies.

This study aimed to use one strain many compounds approach (OSMAC) to investigate the cytotoxic potential of Aspergillus terreus associated with soybean versus several cancer cell lines, by means of in-silico and in vitro approaches. Fermentation of the isolated strain was done on five media. The derived extracts were investigated for their inhibitory activities against three human cancer cell lines; mammary gland breast cancer (MCF-7), colorectal adenocarcinoma (Caco-2), and hepatocellular carcinoma (HepG2) using MTT Assay. The fungal mycelia fermented in Modified Potato Dextrose Broth (MPDB) was the most cytotoxic extract against HepG2, MCF-7, and Caco-2 cell lines with IC50 4.2±0.13, 5.9±0.013 and 7.3±0.004μg mL-1, respectively. MPDB extract was scaled up resulting in the isolation of six metabolites; three fatty acids (1, 2, and 4), one sterol (3) and two butenolides (5 and 6) by column chromatography. The isolated compounds (1-6) were screened through a molecular docking approach for their binding aptitude to various active sites. butyrolactone-I (5) revealed a significant interaction within the CDK2 active site, while aspulvinone E (6) showed promising binding affinity to FLT3 and EGFR active sites that was confirmed by in vitro CDK2, FLT3 and EGFR inhibitory activity. Finally, the in vitro cytotoxic activities of butyrolactone-I (5) and aspulvinone E (6) revealed the antiproliferative activity of butyrolactone-I (5), against HepG2 cell line (IC50=17.85±0.32μM). Molecular docking analysis and in vitro assays suggested the CDK2/A2 inhibitory potential of butyrolactone-I (5) in addition to the promising interaction abilities of aspulvinone E (6) with EGFR and FLT3 active sites as a possible mechanism of their biological activities.

Synthesis, Reactivity, and Anticancer Activity Evaluation of 4‐Amino‐3‐Mercapto‐6‐Methyl‐1,2,4‐Triazin‐5(4H)‐One Derivatives

Abstract1,2,4‐Triazine and its derivatives occupy a fundamental position in the field of medicinal chemistry because of their diverse biological applications, such as anticancer. To search for promising anticancer agents, a new series of 4‐amino‐3‐mercapto‐6‐methyl‐1,2,4‐triazin‐5(4H)‐one derivatives was prepared. Straightforward synthetic methodologies were employed, such as condensation, cyclization, hydrazinolysis, alkylation, and condensation‐addition reactions. All of the new compounds were characterized by a combination of spectral data and elemental analysis. The molecular structures of several compounds on a single crystal X‐ray provided confirmation. The anticancer activity was evaluated against three cancer cell lines, which are hepatocellular carcinoma (HEPG‐2), colorectal carcinoma (HCT‐116) and mammary gland breast cancer (MCF‐7). The results revealed that a representative number of compounds have potent cytotoxicity against HEPG‐2, HCT‐116 and MCF‐7 cell lines with IC50 values ranging from 6.71 to 31.25 μg/mL.

A combined crystallographic and theoretical investigation of noncovalent interactions in 1,3,4-oxadiazole-2-thione-N-Mannich derivatives: in vitro bioactivity and molecular docking.

Two 1,3,4-oxadiazole-2-thione-N-Mannich derivatives, specifically 5-(4-chlorophenyl)-3-[(2-trifluoromethylphenylamino)methyl]-1,3,4-oxadiazole-2(3H)-thione (1) and 5-(4-chlorophenyl)-3-[(2,5-difluorophenylamino)methyl]-1,3,4-oxadiazole-2(3H)-thione (2), were synthesized and then characterized by elemental analysis and NMR (1H and 13C) spectroscopy and the single crystal X-ray diffraction method. The formed weak intermolecular interactions in the solid-state structures of these derivatives were thoroughly investigated utilizing a variety of theoretical tools such as Hirshfeld surface analysis and quantum theory of atoms in molecules (QTAIM). Furthermore, the CLP-PIXEL and density functional theory calculations were used to study the energetics of molecular dimers. Numerous weak intermolecular interactions such as C-H⋯S/Cl/F/π interactions, a directional C-Cl⋯Cl halogen bond, π-stacking, type C-F⋯F-C contact and a short F⋯O interaction, help to stabilize the crystal structure of 1. Crystal structure 2 also stabilizes with several weak intermolecular contacts, including N-H⋯S, C-H⋯N//Cl/F interactions, a highly directional C1-Cl1⋯C(π) halogen bond and C(π)⋯C(π) interaction. In vitro antimicrobial potency of compounds 1 and 2 was assessed against various Gram-positive and Gram-negative bacterial strains and the pathogenic yeast-like Candida albicans. Both compounds showed marked activity against all tested Gram-positive bacteria and weak activity against Escherichia coli and lacked inhibitory activity against Pseudomonas aeruginosa. In addition, compounds 1 and 2 displayed good in vitro anti-proliferative activity against hepatocellular carcinoma (HepG-2) and mammary gland breast cancer (MCF-7) cancer cell lines. Molecular docking studies revealed the binding modes of title compounds at the active sites of prospective therapeutic targets.

Human dihydrofolate reductase inhibition effect of 1-Phenylpyrazolo[3,4–d]pyrimidines: Synthesis, antitumor evaluation and molecular modeling study

A new series of pyrazolo[3,4–d]pyrimidine analogues bearing different amino acid conjugates 10a-m were synthesized with the aim to evaluate their antitumor effect through simultaneous inhibition of human dihydrofolate reductase (hDHFR). All novel compounds were tested to screen their enzyme inhibition activity against (hDHFR) beside their in vitro cytotoxicity against six human MTX resistant cancer cell lines namely, human prostate cancer (PC-3), pancreatic human cancer cell lines (BxPC-3), colorectal carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), cervical carcinoma (HeLa), and mammary gland breast cancer (MCF-7), besides normal immortalized pancreatic cell line (HPDE). Compounds 10e, 10f, 10g inhibited DHFR at considerable low (IC50 < 1 µM) in comparison to MTX (IC50 = 5.61 µM) beside their characteristic cytotoxic effects on different resistant cancer cell lines. Flow cytometry was done for the most active candidate compound 10e against MCF-7 breast cancer cell line. The results illustrated that compound 10e induced apoptosis and arrested MCF-7 cell cycle in the G1/S phase. Western blot for visualization and quantification was used to confirm the capability of compound 10e to induce the expression of proapoptotic caspases and Bax proteins in MCF-7 breast cancer cell line beside its ability to reduce the expression of antiapoptotic Bcl-2 protein. Molecular modeling studies demonstrated that compound 10e elucidated binding energy of (S= − 8.4390 Kcal/mol) that exceed that of the normal ligand MTX (S= − 8.3951Kcal/mol) in addition to several favorable binding interactions with the active site residues.

Design, synthesis and computational study of new benzofuran hybrids as dual PI3K/VEGFR2 inhibitors targeting cancer

Design and synthesis of a new series of benzofuran derivatives has been performed. 1H-NMR, 13C-NMR, elemental analysis, and IR were used to confirm the structures of the produced compounds. Hepatocellular carcinoma (HePG2), mammary gland breast cancer (MCF-7), epithelioid carcinoma cervical cancer (Hela), and human prostate cancer are used to test anticancer activity (PC3). In compared to DOX (4.17–8.87 µM), Compound 8 demonstrated the highest activity against HePG and PC3 cell lines, with an IC50 range of 11–17 µM. Compound 8 inhibited PI3K and VEGFR-2 with IC50 values of 2.21 and 68 nM, respectively, compared to 6.18 nM for compound LY294002 and 31.2 nM for compound sorafenib as PI3K and VEGFR-2 reference inhibitors, selectively. The molecular docking and binding affinity of the generated compounds were estimated and studied computationally utilizing molecular operating environment software as a PI3K and VEGFR-2 inhibitor (MOE). In conclusion, compound 8 exhibited significant action against hepatocellular and cervical cancer cell lines. Mechanistic study showed that it had a dual inhibitory effect against PI3K and VEGFR-2.

Synthesis and Anticancer Evaluation of New Thiazole and Thiadiazole Derivatives Bearing Acetanilide Moiety.

New thiazole and thiadiazole derivatives bound to the acetanilide moiety were synthesized and evaluated for their cytotoxic activity. The precursor N-(4-acetamidophenyl)-N'-phenylthiourea (2) was cyclocondensed with ethyl bromoacetate to afford a mixture of the two isomers, 2-(4-acetamidophenylimino)-3-phenylthiazolidin-4-one (3a, 23%) and 3-(4-acetamidophenyl)-2-phenyliminothiazolidin-4-one (3b, 71%). The Knoevenagel reaction of 3b with various aromatic aldehydes afforded 5-arylidene-2-phenyliminothiazolidin-4-one derivatives 5a-5e. Intramolecular cyclization of thiourea scaffold 2 with chloroacetone and/or phenacyl chloride gave the conforming thiazole derivatives 6a and 6b. A new series of thiadiazole derivatives 9a-9c and 11a-11c was synthesized by the reaction of N-(4-acetamidophenyl)-N'-phenylthiourea (2) with selected derivatives of hydrazonoyl halide in ethanol and triethylamine. The structures of the synthesized thiazole and thiadiazole compounds were elucidated by their compatible spectral data. The cytotoxic activity of the synthesized thiazole and thiadiazole derivatives was screened against four human cancer cell lines and showed promising results. Thiazolidin-4-one compound 5d showed the strongest cytotoxic effects on hepatocellular carcinoma (IC50 = 8.80 ± 0.31 μg/mL), mammary gland breast cancer (IC50 = 7.22 ± 0.65 μg/mL) and colorectal carcinoma (IC50 = 9.35 ± 0.61 μg/mL) cell lines.

Design, synthesis and chemoinformatic studies of new thiazolopyrimidine derivatives as potent anticancer agents via phosphodiesterase-5 inhibition and apoptotic inducing activity

Inhibition of phosphodiesterase-5 (PDE5) has been validated as possible new therapeutic approach for cancer. To further explore this concept, three series of thiazolopyrimidine containing compounds has been designed and synthesized as PDE5 inhibitors. All the compounds were evaluated against PDE5 inhibitory effect in addition to their antiproliferative activities against three different cancer cell lines (colorectal carcinoma colon cancer; HCT-116, mammary gland breast cancer; MCF-7 and human prostate cancer; PC3) in addition to normal cell line (human lung fibroblast; WI38). Among the synthesized compounds, three compounds (3c, 4a and 5a) significantly inhibit PDE5 with IC50 0.046 nM, 0.323 nM, and 0.546 nM, respectively in comparison to sildenafil (IC50 0.689 nM). Moreover, compounds 3a, 3c, 3f, 3g, 3h were found to have potent cytotoxic activities against MCF-7 cancer cell line with IC50 ranging from 5.47±0.4 to 9.92±0.9 µM. Apoptosis cytometric assay showed that compound 5a induced pronounced increase in the total percent of apoptotic HCT116 cells (15.87%) compared to 3c (12.43%), mainly during late stage. Additionally, compounds 3c and 5a were evaluated against proapoptotic Bax, and anti-apoptotic Bcl-2 expression levels that revealed that both compounds expressively enhanced Bax 7.68 and 5.42 folds, respectively compared to untreated control. Also, both compounds 3c and 5a down regulate Bcl-2 with 2.94 and 2.354 ng/mL, respectively. From the docking study, it was concluded that compounds 3c and 5a interact in a similar pattern to sildenafil in the binding site of PDE5. Finally, logP and in silico ADMET assessment were calculated to determine the lipohpilcity metric and ADMET properties for these candidates.

Formulation, characterization and in-vitro evaluation of solid lipid nanoparticles for the delivery of a new anticancer agent, 1H-pyrazolo[3,4-d] pyrimidine derivative

&#x0D; &#x0D; &#x0D; &#x0D; Purpose: To investigate the physicochemical properties and in vitro cytotoxic effect of a potent epidermal growth factor receptor-tyrosine kinase (EGFRWT-TK) inhibitor, 1H-pyrazolo [3,4-d] pyrimidine (FEP) derivative and formulated as solid lipid nanoparticles (SLNs) using stearic acid (ST) or glycerylmonostearate (GMS).&#x0D; Methods: The SLNs were prepared by hot homogenization and sonication method. The effect of formulation variables on particle size, zeta potential and polydispersity index (PDI) of SLNs were studied, and an optimized formulation selected. Drug-excipient interactions were assessed by differential scanning calorimetry (DSC) and Fourier Transform Infrared (FTIR). Mammary gland breast cancer (MCF-7) and human colon cancer (HCT116) human cell lines were used to evaluate the cytotoxic activity of the free and FEP-loaded SLNs.&#x0D; Results: The particle size of the SLNs was in the range of 138 - 819 nm, while zeta potential varied from -15 to -20 nm. FEP-loaded SLNs exhibited significant cytotoxic effect compared to the free drug and doxorubicin in the two cell lines (p &lt; 0.05). The activity was higher in HCT116 compared with MCF-7 cells (p &lt; 0.007). The concentration of FEP loaded SLNs, free drug and doxorubicin that showed 50 % inhibition (IC50) for breast cancer cells were 1.06 ± 0.09, 2.58 ± 0.16 and 3.75 ± 0.4 μg/ml, respectively.&#x0D; Conclusion: The findings show that FEP-loaded SLNs have greater in-vitro cytotoxic activity than the free FEP, and thus, might improve cancer therapy in humans.&#x0D; &#x0D; &#x0D; &#x0D;

Magnetic resonance imaging of tumor-associated-macrophages (TAMs) with a nanoparticle contrast agent.

In the tumor micro-environment, tumor associated macrophages (TAMs) represent a predominant component of the total tumor mass, and TAMs play a complex and diverse role in cancer pathogenesis with potential for either tumor suppressive, or tumor promoting biology. Thus, understanding macrophage localization and function are essential for cancer diagnosis and treatment. Typically, tissue biopsy is used to evaluate the density and polarization of TAMs, but provides a limited “snapshot” in time of a dynamic and potentially heterogeneous tumor immune microenvironment. Imaging has the potential for three-dimensional mapping; however, there is a paucity of macrophage-targeted contrast agents to specifically detect TAM subtypes. We have previously found that sulfated-dextran coated iron oxide nanoparticles (SDIO) can target macrophage scavenger receptor A (SR-A, also known as CD204). Since CD204 (SR-A) is considered a biomarker for the M2 macrophage polarization, these SDIO might provide M2-specific imaging probes for MRI. In this work, we investigate whether SDIO can label M2-polarized cells in vitro. We evaluate the effect of degree of sulfation on uptake by primary cultured bone marrow derived macrophages (BMDM) and found that a higher degree of sulfation led to higher uptake, but there were no differences across the subtypes. Further analysis of the BMDM showed similar SR-A expression across stimulation conditions, suggesting that this classic model for macrophage subtypes may not be ideal for definitive M2 subtype marker expression, especially SR-A. We further examine the localization of SDIO in TAMs in vivo, in the mammary fat pad mouse model of breast cancer. We demonstrate that uptake by TAMs expressing SR-A scales with degree of sulfation, consistent with the in vitro studies. The TAMs demonstrate M2-like function and secrete Arg-1 but not iNOS. Uptake by these M2-like TAMs is validated by immunohistochemistry. SDIO show promise as a valuable addition to the toolkit of imaging probes targeted to different biomarkers for TAMs.

An effective green one-pot synthesis of some novel 5-(thiophene-2-carbonyl)-6-(trifluoromethyl)pyrano[2,3-c]pyrazoles and 6-(thiophene-2-carbonyl)-7-(trifluoromethyl)pyrano[2,3-d]pyrimidines bearing chromone ring as anticancer agents

An effective green one-pot and catalyst-free synthesis of a series of novel 5-(thiophene-2-carbonyl)-6-(trifluoromethyl)pyrano[2,3-c]pyrazoles and 6-(thiophene-2-carbonyl)-7-(trifluoromethyl)pyrano[2,3-d]pyrimidines bearing chromone ring was achieved. The method depended on a one-pot three-component reaction of readily available starting materials 4-oxo-4H-chromene-3-carboxaldehyde, 2-thenoyltrifluoroacetone, and cyclic active methylene compounds in water as solvent. The targeted compounds were assessed for their in vitro anticancer activity against mammary gland breast cancer cell line (MCF-7), liver cancer (HepG-2), and human colon cancer (HCT-116) by using sulphorhodamine B assay (SRB) method, while doxorubicin, was utilized as standard reference drug. Compounds 4a, 4c, and 6b exhibited excellent anticancer activity versus all cancer cell lines with IC50 values ranging from 1.7 to 9.9 μg/mL.

SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF SOME NEW 1,2,4-TRIAZOLO QUINAZOLINE DERIVATIVES

Cancer is a major public health problem in all countries and remains as one of the top leading causes of death worldwide. Herein we report the synthesis of novel series of triazoloquinazolines as potential anticancer agents. Structures of this set of compounds were confirmed by different spectral data including IR, 1H NMR, 13C NMR, Mass spectra, and elemental analyses. All the newly synthesized compounds were evaluated for their anti-proliferative activity against four human cancer cell lines namely; Hepatocellular carcinoma (HePG-2), Mammary gland breast cancer (MCF-7), Human prostate cancer (PC3) and Colorectal carcinoma (HCT-116)). Results of cytotoxicity evaluation showed that the synthesized compounds displayed moderate cytotoxic activity against the selected cancer cell lines. Compound 9 showed the highest anti-proliferative effect followed by compound 7 against colorectal carcinoma cell line (HCT-116) with IC50 values of 17.35 and 27.05 µM respectively. As well, both compounds showed moderate activity against hepatocellular carcinoma (HePG2) with IC50 values of 29.47 and 39.41 µM respectively.

Synthesis of 4‐Hydroxy‐2‐pyridinone Derivatives and Evaluation of Their Antioxidant/Anticancer Activities

AbstractA simple approach was applied for the regioselective synthesis of various pyridine‐2‐one derivatives or annulated pyridine as novel heterocyclic systems from the reaction of dehydroacetic acid (DHA) with mono‐ or bidentate nucleophile as with benzylamine and/or phenylenediamines in dichloromethane followed by transformation with different halo‐compounds in refluxing 1,4‐dioxane has been achieved in moderate to excellent yields (48‐93 %). In addition, DFT studies of the key synthesized compounds were carried out for confirmed proposed mechanisms. The newly synthesized compounds were screened for their in‐vitro inhibition activities against mammary gland breast cancer (MCF‐7) and human prostate cancer (PC‐3) using the MTT colorimetric method. Also, the target synthesized compounds were evaluated as antioxidant agents.

Reduction of Tumor Vascularity and Aid Excision using Endovascular Embolization

Fresh fruits are considered as a healthy source of water soluble vitamins. Vitamins are needed for metabolic reactions, their deficiency or increased intake lead to different irregularities in normal metabolism. Our work aimed to determine some different types of vitamin B as B1, B6, B2, B9 and B17 and applications of different methods of extracting and analyzing them by HPLC then loading them on chitosan nanoparticles (CSNPs) to study its biological applications and cytotoxicity on different cell lines. HPLC analysis of acid hydrolysis samples showed that thiamine (B1) was found in range of 88.13-96.66 %, riboflavin (B2) was 95 - 96.216 %, pyridoxine (B6) was 95.22 - 100 %, folate (B9) 95.6-96.94 % while amygdalin (B17) was 94.975-96.66 %. After loading vitamins with chitosan, the results showed cytotoxic activities of Vitamins B1, B2, B6, B9 and B17 as these extracted vitamins were tested against different cancerous and normal cell lines. Vitamin B6 nanoparticles showed the best cytotoxic effect on different cancerous cell lines as Hepatocelluar carcinoma (HePG2), Mammary gland Breast cancer (MCF-7) and Epitheliod Carcinoma Cervix cancer (Hela) and it can be considered as a safe compound on normal cell as normal human lung fibroblast cell line (WI-38).

Antitumor Activity of Normal and Chitosan Nanoparticles Loaded with Different Extracted Vitamin B Types

Fresh fruits are considered as a healthy source of water soluble vitamins. Vitamins are needed for metabolic reactions, their deficiency or increased intake lead to different irregularities in normal metabolism. Our work aimed to determine some different types of vitamin B as B1, B6, B2, B9 and B17 and applications of different methods of extracting and analyzing them by HPLC then loading them on chitosan nanoparticles (CSNPs) to study its biological applications and cytotoxicity on different cell lines. HPLC analysis of acid hydrolysis samples showed that thiamine (B1) was found in range of 88.13-96.66 %, riboflavin (B2) was 95 - 96.216 %, pyridoxine (B6) was 95.22 - 100 %, folate (B9) 95.6-96.94 % while amygdalin (B17) was 94.975-96.66 %. After loading vitamins with chitosan, the results showed cytotoxic activities of Vitamins B1, B2, B6, B9 and B17 as these extracted vitamins were tested against different cancerous and normal cell lines. Vitamin B6 nanoparticles showed the best cytotoxic effect on different cancerous cell lines as Hepatocelluar carcinoma (HePG2), Mammary gland Breast cancer (MCF-7) and Epitheliod Carcinoma Cervix cancer (Hela) and it can be considered as a safe compound on normal cell as normal human lung fibroblast cell line (WI-38).

Synthesis, anticancer and antimicrobial evaluation of new benzofuran based derivatives: PI3K inhibition, quorum sensing and molecular modeling study

A new series of benzofuran derivatives has been designed and synthesized. The structures of the synthesized compounds have been confirmed by the use of 1H NMR, 13C NMR, 2D 1H–1H NOESY NMR, and IR. Anticancer activity is evaluated against Hepatocellular carcinoma (HePG2), mammary gland breast cancer (MCF-7), Epitheliod carcinoma cervix cancer (Hela) and human prostate cancer (PC3). Compounds 8, 9, and 11 showed the highest activity towards the four cell lines with an IC50 range of 8.49–16.72 µM, 6.55–13.14 µM and 4–8.99 µM respectively in comparison to DOX (4.17–8.87 µM). Phosphatidylinositol-3-kinases (PI3K) inhibition was evaluated against the most active anticancer compounds 8, 9 and 11. Compounds 8, 9 and 11 showed good inhibitory activity against PI3Kα with IC50 values 4.1, 7.8, and 20.5 µM, respectively in comparison to 6.18 µM for the reference compound LY294002. In addition, activity of compounds 8 and 9 on cell cycle arrest and induction of apoptosis in different phases of MCF-7 cells were assessed and detected pre-G1 apoptosis and cell growth arrest at G2/M. Also, both extrinsic and intrinsic apoptosis in MCF-7 cells induced by compounds 8 and 9. Molecular docking, binding affinity surface mapping, and contact preference of the synthesized compounds 8, 9 and 11 against PI3K were estimated and studied computationally using molecular operating environment software (MOE) and showed good interaction with essential residues for inhibition Val851. In addition, antimicrobial activity was evaluated against gram positive isolates as Staphylococcus aureus and Bacillus cereus, gram negative isolate as Escherichia coli, Pseudomonas aeruginosa and antifungal potential against Candida albicans. Compound 17 showed outstanding anti Gram-positive activity with MIC values 8 and 256 µg/mL in Staphylococcus aureus and Bacillus cereus respectively. Also, compounds 15, 17, 18 and 21 showed good anti Gram-negative activity with MIC value 512 µg/mL for all compounds. In addition, the state-of-art quorum sensing (QS) inhibiting effects were detected using Chromobacterium violaceum and compounds 7, 9, 10, 11, and 12 showed good QS inhibition (3, 3, 5, 2, and 7 mm).