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In this study, five known meroterpenoids sargaol (1), flabellinone (2), stypodiol (3), atomarianone A (4), atomarianone B (5), and a known steroid fucosterol (6) were isolated from brown alga Stypopodium schimperi. Their structures were elucidated by 1D- and 2D NMR and mass spectroscopic analyses. Isolated compounds were tested against human healthy fibroblast cells (CCD-1079Sk), and two different types of human breast cancer cell lines (MDA-MB-231 and MCF-7). They were also investigated by molecular docking studies on estrogen receptor alpha (ERα), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2), cyclin-dependent kinases 2, 4 and 6 (CDK2/4/6) proteins. Molecular dynamics simulations were carried out to determine their ligand-protein stability and binding affinity. The four isolates (1 - 3 , 6) showed strong cytotoxic activity in vitro against both cancer cell lines, particularly the aggressive MDA-MB-231 cell line, which was verified by in silico screening. Fucosterol was found to be the most selective compound against cancer cell lines, particularly the aggressive MDA-MB-231 cell line with a selectivity index (SI>16). The ADME prediction was also carried out and all the isolate compounds showed drug likeness. As a result, stypodiol and fucosterol were found to be the most potent compounds against both cancer cell lines by in vitro and in silico studies. [Display omitted] • Five meroterpenoids and one steroid were isolated from Stypopodium schimperi for the first time. • Their structures were elucidated by NMR and HRMS. • Isolated compounds were tested against two different cancer cells and an healthy cell lines as in vitro. Stypodiol and Fucosterol were found as potent inhibitors of ERα and HER2, respectively. [ABSTRACT FROM AUTHOR]

• Four mononuclear and dinuclear carboxamide Pd complexes isolated. • Molecular structures confirmed using single crystal X-ray analyses. • Interactions of the Pd complexes with CT-DNA) investigated. • BSA interactions studies established static quenching mechanism. • Cytotoxic effects of the complexes examined in three cancer cell lines. Reactions of ligands [ N 2, N 3-bis(pyridin-2-yl)pyrazine-2,3-dicarboxamide] (L1), [ N 2, N 3-bis(6-methylpyridin-2-yl)pyrazine-2,3-dicarboxamide] (L2), [ N 2, N 3-bis(4-methylpyridin-2-yl)pyrazine-2,3-dicarboxamide] (L3) and [ N 2, N 3-bis(quinoline-8-yl)pyrazine-2,3-dicarboxamide] (L4) with [PdCl 2 (NCMe) 2 ] afforded the respective palladium(II) complexes: [Pd 2 (L1) 2 Cl 2 ] (Pd1) , [Pd 2 (L2) 2 Cl 2 ] (Pd2) , [Pd 2 (L3) 2 Cl 2 ] (Pd3) and [Pd(L4) Cl] (Pd4). Molecular structures of complexes Pd1 and Pd3 are dinuclear containing two bridging bidentate ligand units. The interactions of the palladium complexes (Pd1 - Pd4) with calf thymus DNA (CT-DNA) were monitored using UV–Vis and fluorescence spectroscopy and revealed intercalative binding modes, with intrinsic binding constants (K b) in the order of 106 M−1. Bovine serum albumin (BSA) interaction was evaluated using fluorescence techniques and displayed a static quenching mechanism. The cytotoxic effects of the complexes Pd1-Pd4 were examined against human breast cancer cell lines MCF-7 and MDA-MB-231, and human transformed lung cell line MRC5-SV2 (a model of lung cancer) and its parental normal lung fibroblast cell line MRC5. While the complexes Pd1 and Pd4 showed significant to moderate cytotoxicity against MCF-7 (IC 50 of 11.2 µM and 61.5 µM, respectively), complexes Pd2 and Pd3 were inactive. All the complexes were inactive against the MDA-MB-231 cell line, and Pd2-Pd4 were inactive against the MRC5-SV2 cell line. Compounds Pd1 exhibited lower cytotoxicity against the normal cell line MRC5. [Display omitted] [ABSTRACT FROM AUTHOR]

• A new set of quinolin-4-ylcarbonylhydrazine derivatives having 2-arylamido-3-arylacryloyl moiety has been synthesized. • The newly synthesized derivatives were evaluated for their cytotoxic activity against MDA-MB-231 cancer cells. • Flow cytometric measurements were carried out for the most potent molecule. • Active compound was tested for β-tubulin assembly inhibition. • Mitochondrial membrane potential was assessed for the most active compound. A new set of quinolin-4-ylcarbonylhydrazine derivatives 7a-i and 9a,b bearing 3-arylacryloyl moiety has been synthesized and investigated for their potential anticancer activity. The synthetic protocol involves the following step: the target quinoline derivatives 7a-i and 9a,b appended to the acryloyl moiety were synthesized from quinolin-4-carbohydrazide intermediate with respective ethyl 2-arylamido-3-arylacrylate compounds. The cytotoxic activity study was evaluated using the functional MTT method. The most of target compounds displayed potent cytotoxic activity against MDA-MB-231 cell line. Among them, compounds 7d and 7 h were found to be promising antiproliferative agents with IC 50 values of 4.04 and 1.78 μM, respectively, relative to the effective anticancer drug, Dox (IC 50 = 5.33 μM). Compound 7 h exhibited cytotoxic activity by causing cell cycle to block at G2/M phase in addition to pro-apoptotic effect, as shown by flow cytometric measurement. In addition, the inhibitory action against β-tubulin polymerization was investigated. Finally, compound 7 h diminished the level of mitochondrial potential by almost 2.8-fold compared to control, indicating that the cellular death proceeds through the provoke of the intrinsic mitochondrial pathway of apoptosis. [ABSTRACT FROM AUTHOR]

• A new set of quinolin-4-ylcarbonylhydrazine derivatives having 2-arylamido-3-arylacryloyl moiety has been synthesized. • The newly synthesized derivatives were evaluated for their cytotoxic activity against MDA-MB-231 cancer cells. • Flow cytometric measurements were carried out for the most potent molecule. • Active compound was tested for β-tubulin assembly inhibition. • Mitochondrial membrane potential was assessed for the most active compound. A new set of quinolin-4-ylcarbonylhydrazine derivatives 7a-i and 9a,b bearing 3-arylacryloyl moiety has been synthesized and investigated for their potential anticancer activity. The synthetic protocol involves the following step: the target quinoline derivatives 7a-i and 9a,b appended to the acryloyl moiety were synthesized from quinolin-4-carbohydrazide intermediate with respective ethyl 2-arylamido-3-arylacrylate compounds. The cytotoxic activity study was evaluated using the functional MTT method. The most of target compounds displayed potent cytotoxic activity against MDA-MB-231 cell line. Among them, compounds 7d and 7 h were found to be promising antiproliferative agents with IC 50 values of 4.04 and 1.78 μM, respectively, relative to the effective anticancer drug, Dox (IC 50 = 5.33 μM). Compound 7 h exhibited cytotoxic activity by causing cell cycle to block at G2/M phase in addition to pro-apoptotic effect, as shown by flow cytometric measurement. In addition, the inhibitory action against β-tubulin polymerization was investigated. Finally, compound 7 h diminished the level of mitochondrial potential by almost 2.8-fold compared to control, indicating that the cellular death proceeds through the provoke of the intrinsic mitochondrial pathway of apoptosis. [ABSTRACT FROM AUTHOR]

• Synthesis, structural studies & application of Schiff base 1 and its Zn(II)-complex 2. • Complex 2 shows better effect in vitro cytotoxicity as compared to 1 Against MDA-MB-231 cell line. • Chromone-appended 1 acts as an exceptionally selective colorimetric receptor for Cu2+. • Complex 2 serves as ultrasensitive fluorescent probe for Ag+ and Fe3+ distinctly. • Interaction with Ag+ forms [2·Ag(NO3)]n and Fe3+ forms [2·{Fe(NO3)2H2O)}2] complex. • Comprehensive DFT studies have been carried out to validate the mechanism and binding. Present article delineates the design and synthesis of a chromone-appended Schiff base (1) and its complexes with Zn(II) (2) and Cu(II) (3), which have been characterized by various spectro-analytical techniques i.e., elemental analysis, FTIR, 1H & 13C NMR, ESI-MS, UV−vis and fluorescence. Structures of 1 and 3 have also been elucidated using single crystal X-ray diffraction analysis. Compounds 2 showed significant effect in vitro cytotoxicity as compared to 1 Against MDA−MB-231 cell line. Interestingly, 1 serves as a chromogenic sensor for Cu2+ with exceptional selectivity whereas, 2 serves as an ultrasensitive fluorescent probe for Ag+ and Fe3+ in mixed aqueous−ethanol. The presence of Ag+ causes ratiometric change in the fluorescence spectral feature of 2 whereas Fe3+ induces ' turn-off ' fluorescence in 2. Probe−analyte binding stoichiometry suggested by Job's plot analysis, ESI−MS and DFT studies, has been found to be 1:1 for 1 with Cu2+ and 2 with Ag+ whereas, 1:2 between 2 and Fe3+. Based on diverse analyses and binding constants, it is observed that 2 offers higher selectivity toward Ag+ over Fe3+. Limit of detection (LoD) of 1 for Cu2+ and 2 for Ag+ and Fe3+ have been found to be 2.33 nM, 22.4 µ M and 2.05 µ M, respectively. Complexes 2 +Ag+ and 2 +Fe3+ characterized by ESI−MS whereas DFT studies have been carried out to investigate the deeper bonding insights and provide support in our experimental investigations. Further, detection of Ag+ and Fe3+ has been practically accomplished in real water samples using probe 2. [Display omitted] Present research entails synthesis, characterization and structural validation along with anticancer activities, UV−vis and fluorescent detection studies of chromone−based probes 1 and 2 toward colorimetric recognition of Cu2+ and ultrafast fluorescent detection of Ag+ and Fe3+ with excellent reusability and LoDs. Both 1 and 2 exhibits anti-cancer properties Against MDA−MB-231 cell line. Detailed DFT studies to support the experimental results and practical application in real water samples have also been accomplished. [ABSTRACT FROM AUTHOR]

• Synthesis, structural studies & application of Schiff base 1 and its Zn(II)-complex 2. • Complex 2 shows better effect in vitro cytotoxicity as compared to 1 Against MDA-MB-231 cell line. • Chromone-appended 1 acts as an exceptionally selective colorimetric receptor for Cu2+. • Complex 2 serves as ultrasensitive fluorescent probe for Ag+ and Fe3+ distinctly. • Interaction with Ag+ forms [2·Ag(NO3)]n and Fe3+ forms [2·{Fe(NO3)2H2O)}2] complex. • Comprehensive DFT studies have been carried out to validate the mechanism and binding. Present article delineates the design and synthesis of a chromone-appended Schiff base (1) and its complexes with Zn(II) (2) and Cu(II) (3), which have been characterized by various spectro-analytical techniques i.e., elemental analysis, FTIR, 1H & 13C NMR, ESI-MS, UV−vis and fluorescence. Structures of 1 and 3 have also been elucidated using single crystal X-ray diffraction analysis. Compounds 2 showed significant effect in vitro cytotoxicity as compared to 1 Against MDA−MB-231 cell line. Interestingly, 1 serves as a chromogenic sensor for Cu2+ with exceptional selectivity whereas, 2 serves as an ultrasensitive fluorescent probe for Ag+ and Fe3+ in mixed aqueous−ethanol. The presence of Ag+ causes ratiometric change in the fluorescence spectral feature of 2 whereas Fe3+ induces ' turn-off ' fluorescence in 2. Probe−analyte binding stoichiometry suggested by Job's plot analysis, ESI−MS and DFT studies, has been found to be 1:1 for 1 with Cu2+ and 2 with Ag+ whereas, 1:2 between 2 and Fe3+. Based on diverse analyses and binding constants, it is observed that 2 offers higher selectivity toward Ag+ over Fe3+. Limit of detection (LoD) of 1 for Cu2+ and 2 for Ag+ and Fe3+ have been found to be 2.33 nM, 22.4 µ M and 2.05 µ M, respectively. Complexes 2 +Ag+ and 2 +Fe3+ characterized by ESI−MS whereas DFT studies have been carried out to investigate the deeper bonding insights and provide support in our experimental investigations. Further, detection of Ag+ and Fe3+ has been practically accomplished in real water samples using probe 2. [Display omitted] Present research entails synthesis, characterization and structural validation along with anticancer activities, UV−vis and fluorescent detection studies of chromone−based probes 1 and 2 toward colorimetric recognition of Cu2+ and ultrafast fluorescent detection of Ag+ and Fe3+ with excellent reusability and LoDs. Both 1 and 2 exhibits anti-cancer properties Against MDA−MB-231 cell line. Detailed DFT studies to support the experimental results and practical application in real water samples have also been accomplished. [ABSTRACT FROM AUTHOR]

Abstract A phytochemical study on the stem bark of Metasequoia glyptostroboides led to the isolation of sixty-one diterpenoids and sesquiterpenoids, including seventeen previously undescribed compounds, metaglyptins A-Q. Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, and 1H, 13C and 2D NMR). The absolute configurations of metaglyptins I, J, and O were determined by the ECD data and single-crystal X-ray diffraction analysis. The undescribed compounds were evaluated for their cytotoxicity against HeLa, AGS, and MDA-MB-231 cancer cell lines. The results revealed that metaglyptin A exhibited moderate cytotoxicity against MDA-MB-231 cell line with IC 50 value of 20.02 μ M. Graphical abstract Seventeen previously undescribed diterpenoids and sesquiterpenoids, as well as forty-four known compounds, were isolated and structurally characterized from the stem bark of Metasequoia glyptostroboides. The isolated undescribed compounds were evaluated for their cytotoxic activity. Image 1 Highlights • Seventeen undescribed terpenoids were isolated from Metasequoia glyptostroboides. • Forty-four known diterpenoids and sesquiterpenoids were isolated. • Metaglyptin A exhibited moderate cytotoxicity against MDA-MB-231 cell line. [ABSTRACT FROM AUTHOR]

Progressive incidence and a pessimistic survival rate of breast cancer in women worldwide remains one of the most concerning topics. Progressing research indicates a potentially high effectiveness of use cold atmospheric plasma (CAP) systems. The undoubted advantage seems its simplicity in combination with other anti-cancer modalities. Following observed trend of studies, one inventory CAP system was applied to directly treat human breast cancer cell lines and culturing in two different Plasma Activated Media (PAM) for combined utilization. Proposed CAP treatments on MCF-10 A, MCF-7, and MDA-MB-231 cell lines were studied in terms of impact on cell viability by MTT assay. Disturbances in cell motility following direct and combined CAP application were assessed by scratch test. Finally, the induction of apoptosis and necrosis was verified with annexin V and propidium iodide staining. Reactive species generated during CAP treatment were determined based on optical emission spectrometry analysis along with colorimetric methods to qualitatively assess the NO 2 −, NO 3 −, H 2 O 2 , and total ROS with free radicals concentration. The most effective approach for CAP utilization was combined treatment, leading to significant disruption in cell viability, motility and mostly apoptosis induction in breast cancer cell lines. Determined CAP dose allows for mild outcome, showing insignificant harm for the non-cancerous MCF-10 A cell line, while the highly aggressive MDA-MB-231 cell line shows the highest sensitivity on proposed CAP treatment. Direct CAP treatment seems to drive the cells into the sensitive state in which the effectiveness of PAM is boosted. Observed anti-cancer response of CAP treatment was mostly triggered by RNS (mostly NO 2 − ions) and ROS along with free radicals (such as H 2 O 2 , OH•, O 2 -•, 1O 2 , HO 2 •). The combined application of one CAP source represent a promising alternative in the development of new and effective modalities for breast cancer treatment. [Display omitted] • Innovative CAP system used for direct and combined treatment of human breast cancer cells. • CAP significantly reduces viability and motility of breast cancer cells and induces their apoptosis. • Direct CAP treatment sensitizes breast cancer cells on the PAM usage. • Anti-cancer activity of CAP was triggered by reactive oxygen and nitrogen species. [ABSTRACT FROM AUTHOR]

Four new limonoids, 7,12-dihydroxyvilasinone (1), vilasindione (2), 4-dehydroxynimbandiol (3) and azadiramide B (4), were isolated from extracts of Bacillus subtilis -fermented neem seeds. Their planar structures and relative configurations were elucidated by spectroscopic methods including UV, IR, MS and NMR, and the absolute stereochemistry was determined by comparing their experimental and calculated CD spectra. 4 is a rare salannin-class limonoid alkaloid. In cytotoxic assays, 3 showed inhibitory activity against MDA-MB-231, A375 and Hela cell lines with IC 50 values of 21.45 ± 5.41, 17.67 ± 3.96 and 28.13 ± 9.12 μM, respectively, while 4 selectively inhibited growth of MDA-MB-231 cell line with an IC 50 value of 15.73 ± 6.07 μM. Unlabelled Image [ABSTRACT FROM AUTHOR]

[Display omitted] • Wedelolactone, a plant compound, was loaded-poly (lactic-co-glycolic acid) into the synthesized NPs against breast cancer and bacteria. • WDL PLGA-NPs characterization by FTIR, XRD, DLS and TEM. • A better antimicrobial effect has been achieved by WDL PLGA-NPs. • WDL PLGA-NPs were significantly cytotoxicity in breast cancer cells. We synthesized a novel wedelolactone-loaded poly-lactic- co -glycolic acid nanoparticle (WDL-PLGA NPs) and evaluated its antibacterial and induce cytotoxicity against breast cancer MDA-MB-231 cell line growth. The physicochemical properties of the WDL-PLGA NPs were defined by Fourier transform infrared spectroscopy (FTIR), and dynamic scattering scanning (DLS) analyzer, and transmission microscopy (TEM) were analysis. FTIR results showed that functional groups of WDL were involved in stabilizing as capping agents. The WDL-PLGA-NPs were spherical shaped with a crystallinity of 53.1 nm in average sizes and a surface charge of −33.0 mV predicted from TEM and zeta potential, respectively. WDL-PLGA NPs exhibit significant antibacterial activity against Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia , and Pseudomonas aeruginosa. The half-inhibitory concentration (IC 50) of the formulated WDL-PLGA NPs was 23 μg/ml but 57 μg/ml in WDL in the breast cancer MDA-MB-231 cell line. The apoptotic effect, nuclear condensation, ROS generation, the loss of mitochondrial membrane potential (Δψm) of WDL-PLGA NPs were analyzed. Thus, WDL-PLGA NPs reduced the levels of Bcl-2 but increased the levels of Bax, which results in driving the cells to undergo apoptosis. Thus, the WDL-PLGA NPs were biocompatible with antibacterial and anticancer properties. [ABSTRACT FROM AUTHOR]

The complexes [Ru(Tyr-)(dppe) 2 ]Cl (1) and [Ru(Ser-)(dppe) 2 ]Cl (2) [Tyr = 8tyrosinate; Ser = 8serinate; dppe = 81,2-bis(diphenylphosphino)ethane] were synthesized and their in vitro cytotoxicities against the MDA-MB-231 cell line were determined by MTT assay. In vivo toxicity assessment on zebrafish embryos showed that although the higher concentration of complex (1) has caused lethality of embryos, the effects of the concentration equivalent to the IC 50 of complex (1) and cisplatin were similar in the hatching rate, mortality rate and morphological changes. [Display omitted] Reaction of α-amino acids (HL) with the precursor cis -[RuCl 2 (dppe) 2 ] [HL = tyrosine (Tyr) or serine (Ser); dppe = 1,2-bis(diphenylphosphino)ethane] afforded the complexes [Ru(L−)(dppe) 2 ]Cl {[Ru(Tyr-)(dppe) 2 ]Cl (1) and [Ru(Ser-)(dppe) 2 ]Cl (2)}. The new ruthenium complexes, with formulae [Ru(Tyr-)(dppe) 2 ]Cl (1) and [Ru(Ser-)(dppe) 2 ]Cl (2) were synthesized and characterized on the basis of elemental analysis, molar conductivity, IR/UV–Vis and 31P{1H} NMR spectra. The in vitro cytotoxicities of the complexes against the MDA-MB-231 (breast adenocarcinoma) cell line were determined by the MTT assay. Complexes (1) and (2) show good cytotoxicity profiles against the MDA-MB-231 cell line with IC 50 values of 2.05 ± 0.71 μM and 5.64 ± 0.72 μM, respectively, which are in the same order of values obtained for the metallodrug cisplatin (2.44 ± 0.20 μM) in the same assay. The selectivity indexes were significant for both complexes, showing lower cytotoxicity activity against the non-tumor breast cell line MCF-10A, with SI of 5.0 and 3.2, respectively. In addition, the lipophilicities of these complexes were determined and their interactions with human serum albumin (HSA) protein were investigated by fluorescence. The lipophilicities of the complexes suggest that this property has a significant effect on their cytotoxicity and the interaction measurements of the complexes with HSA indicate that the static fluorescence quenching mechanism is the main one involved in the formation of (1)-HSA and (2)-HSA adducts. Moreover, Van der Waalś interactions and hydrogen bonds in (1)-HSA and electrostatic interaction in (2)-HSA are the predominant intermolecular forces between the complexes and the biomolecule. Furthermore, the antioxidant activity of the complexes was determined using the superoxide radical scavenging method, in vitro. Complex (1) was found to present a higher antioxidative activity, showing to be better than the standard antioxidant, vitamin C. In vivo toxicity assessment on zebrafish embryos showed that although the higher concentration of complex (1) has caused lethality of embryos, the effects of the concentration equivalent to the IC 50 of complex (1) and cisplatin were similar in the hatching rate, mortality rate and morphological changes, showing a potential of complex (1) as a new anticancer agent. [ABSTRACT FROM AUTHOR]

In this work we present the synthesis and characterization of six new ruthenium compounds with general formulae [Ru(L)(dppb)(bipy)]PF 6 and [Ru(L)(dppe) 2 ]PF 6 where L = salicylic acid (Sal), 4-aminosalicylic acid (AmSal) or 2,4-dihydroxybenzoic acid (DiSal), dppb = 1,4- bis (diphenylphosphino)butane, dppe = 1,2- bis (diphenylphosphino)ethane and bipy = 2,2′-bipyridine. The complexes were characterized by elemental analysis, molar conductivity, cyclic voltammetry, NMR, UV–vis and IR spectroscopies, and two by X-ray crystallography. The 31P{1H} NMR spectra of the complexes with the general formula [Ru(L)(dppe) 2 ]PF 6 showed that the phosphorus signals are solvent-dependent. Aprotic solvents, which form strong hydrogen bonds with the complexes, inhibit the free rotation of the salicylic acid-based, modifying the diphosphine cone angles, leading to distortion of the phosphorus signals in the NMR spectra. The cytotoxicity of the complexes was evaluated in MCF-7, MDA-MB-231, SKBR3 human breast tumor cells, and MCF-10 non-tumor cell lines. The complexes with the structural formula [Ru(L)(dppe) 2 ]PF 6 were the most cytotoxic, and the complex [Ru(AmSal)(dppe) 2 ]PF 6 with L = 4-aminosalicylic acid ligand was the most selective for the MDA-MB-231 cell line. This complex interacts with the transferrin and induces apoptosis through the intrinsic pathway, as demonstrated by increased levels of proteins involved in apoptotic cell death. [Display omitted] • Six Ru(II) complexes of salicylic acid and derivatives were synthesized. • Complex [Ru(AmSal)(dppe) 2 ]PF 6 – Ru(5) was the most selective against TNBC. • Ru(5) inhibited colony formation by acting as a cytotoxic and cytostatic agent. • Ru(5) induced tumor cells apoptosis, altering the mitochondrial membrane potential. • Ru (5) induced cell death through intrinsic apoptotic pathway signaling. [ABSTRACT FROM AUTHOR]

A series of new 4(3 H)-quinazolinones were synthesized and evaluated for their cytotoxic activity against a set of human cancer cell lines MDA-MB-231 and MCF-7 (breast), HCT-116 and HT-29 (colon) and A549 (lung). Among the tested compounds, 22a exhibited promising cytotoxic activity against MDA-MB-231 (IC 50 : 3.21 μ M) and HT-29 (IC 50 : 7.23 μ M) cell lines. The mechanism of action and the apoptosis inducing effect of the compound 22a were studied using the breast cancer cell line MDA-MB-231. Treatment of MDA-MB-231 cell line with compound 22a showed typical apoptotic morphology like cell shrinkage, chromatin condensation and horseshoe shaped nuclei formation. Flow cytometric analysis indicated that the compound induces G0/G1 phase of cell cycle arrest in a dose dependent manner. The binding modes of the potent compounds with EGFR target protein were investigated by docking studies. Image 10440 • New 4(3 H)-Quinazolinones were synthesized and evaluated for anticancer activity. • 22a exhibited promising cytotoxicity against MDA-MB-231 cell line. • Cell growth inhibition and apoptosis inducing effect of 22a were explored. • Flow-cytometry analysis showed the cell cycle arrest in a dose dependent manner. [ABSTRACT FROM AUTHOR]

Three series of indeno[1,2- c ]isoquinolines bearing a ferrocenyl entity were synthesized and evaluated for DNA interaction, topoisomerase I and II inhibition, and cytotoxicity against breast human cancer cell lines. In the first and second series, the ferrocenyl scaffold was inserted as a linker between the two nitrogen atoms. In the last series, it was introduced at the end of the carbon chain. The present study showed that the ferrocenyl entity enhanced the topoisomerase II inhibition. Most compounds showed a potent growth inhibitory effect on MDA-MB-231 cell line with the IC 50 in μM range. [ABSTRACT FROM AUTHOR]

Thirteen novel furoxan-based nitric oxide (NO) releasing hybrids ( 14a–e , 15a–e , 17b–d ) of 16,17-pyrazo-annulated steroidal derivatives were synthesized and evaluated against the MDA-MB-231, HCC1806, SKOV-3, DU145, and HUVEC cell lines for their in vitro anti-proliferative activity. Most of the compounds displayed potent anti-proliferative effects. Among them, 17c exhibited the best activity with IC 50 values of 20–1.4 nM against four cell lines (MDA-MB-231, SKOV-3, DU145, and HUVEC), and 1.03 μM against a tamoxifen resistant breast cancer cell line (HCC1806). Furthermore, five compounds ( 14a , 15a , 17b–d ) were selected to screen for VEGF inhibitory activity. Compounds 15a , 17b , c showed obviously better activity than 2-Methoxyestradiol (2-ME) on reducing levels of VEGF secreted by MDA-MB-231 cell line. In a Capillary-like Tube Formation Assay, compounds 17b , c exhibited a significant suppression of the tubule formation in the concentration of 1.75 nM and 58 nM, respectively. The preliminary SAR showed that steroidal scaffolds with a linker in 3-position were favorable moieties to evidently increase the bioactivities of these hybrids. Overall, these results implied that 17c merited to be further investigated as a promising anti-cancer candidate. [ABSTRACT FROM AUTHOR]

A simple, mild and efficient method for the synthesis of pyrazolopyridine based spirooxindoles by the three-component reaction has been developed using sulfamic acid (H 2 NSO 3 H) as a green catalyst. The method involves use of water as a solvent which makes it eco-friendly. The catalyst used is readily available and is prominent for short reaction time, operational simplicity and high yields. After completion of the reaction the catalyst could be recovered and reused for up to four cycles without loss in catalytic activity. Employing this method a library of 34 compounds has been synthesized and investigated for their cytotoxicity against a panel of three human cancer cell lines. Some of the compounds like 4o and 4p exhibited remarkable cytotoxicities with IC 50 values of 0.35 μM and 1.92 μM against MDA-MB-231 cell line. [ABSTRACT FROM AUTHOR]

Abstract: Successful management of metastatic breast cancer still needs better chemotherapeutic approaches. The combination of fenretinide (4-HPR), a synthetic retinoid inducing apoptosis by ROS generation, and TRAIL, a cell death ligand inducing caspase-dependent apoptosis, might result in more powerful cytotoxic activity. We therefore investigated the cytotoxic activity and resulting cell death mode of this combination in MDA-MB-231 cell line as a representative of metastatic state. Cytotoxicity was assessed by the ATP viability assay while the mode of cell death was determined both morphologically using fluorescence microscopy and biochemically using Western blotting and ELISA. The combination resulted in an additive cytotoxic effect at the doses used. Fragmented and/or pyknotic nuclei, which is a feature of apoptosis, were observed after treatment with fenretinide or TRAIL. However, the combinatorial treatment further increased apoptotic figures. Confirming apoptosis, active caspase-3 and cleaved PARP were increased by fenretinide or TRAIL in both western blotting and ELISA. Again, apoptosis was further increased by the combination. The combination warrants further studies due to its superior cytotoxic activity in the metastatic setting of breast cancer. [Copyright &y& Elsevier]

Abstract: Twenty four compounds with diversified 3-aryl acrylic amide side chains of the simplified saframycin–ecteinascidin pentacyclic skeleton were synthesized via a 14-step stereospecific route starting from l-dopa. The cytotoxicities of these compounds were tested against eight human tumor cell lines including HCT-8, BEL-7402, BGC-803, A549, A2780, MCF-7, MX-1, and MDA-MB-231. Most of these compounds exhibited potent antitumor activity, and a preliminary structure–activity relationship (SAR) was discussed. Compound 28 with 3-thiophenyl acrylic amide side chain exhibited selective cytotoxicity against MDA-MB-231 cell line with the IC50 value of 50 nM. [Copyright &y& Elsevier]

Abstract: Gemcitabine (2′,2′-difluoro-2′-deoxycytidine; dFdCyd) is one of the anti-metabolites drugs that target DNA replication. We evaluated dFdCyd cytotoxicity and its radiosensitizing ability in human breast cancer cell lines, MCF-7 (wild-type p53) and MDA-MB-231 (mutant-type p53) along with normal mammary epithelial cell line (MCF-12) for comparison. Radiosensitivity and cytotoxicity were measured by the clonogenic survival assays. DNA DSBs was studied by Pulse Field Gel Electrophoresis (PFGE) and cell cycle distribution was analyzed by flow cytometry. MDA-MB-231 cells were the most sensitive to the cytotoxicity of dFdCyd (IC50 5nM) then MCF-7 (IC50 10nM), whereas MCF-12 cells were the most resistant to the cytotoxicity of dFdCyd (IC50 70nM). MCF-12 and MCF-7 cell lines did not show any radiosensitization to dFdCyd, whereas the MDA-MB-231 cells showed significantly increased radioresistant to dFdCyd at equimolar concentration (p=0.002) and at IC50 concentration (p<0.001). The DNA double strand breaks (DSBs) repair showed that dFdCyd neither increases DNA DSBs nor decreases the rate of their repair in MCF-12 and MCF-7 cell lines, while the same treatment in MDA-MB-231 cell line led to decrease the rate of DSBs or increase the rate of DNA repair (p=0.034). Therefore, dFdCyd is a cytotoxic agent, especially in the cancer cells irrespective of having wild-type or mutated p53 protein, but it is not effective as radiosensitizer in the cell lines used in this study. dFdCyd combined with radiation reduces the efficacy of chemo-radiotherapy in p53 mutated cells. Therefore, p53-mutated cancer could be a counter-indication for radiation–gemcitabine combined treatment. [Copyright &y& Elsevier]

Abstract: A series of C5-substituted licofelone ([2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]acetic acid) derivatives were developed by a parallel synthesis approach and investigated for cytotoxicity against MCF-7 and MDA-MB-231 cells as well as for anti-inflammatory potency in vitro and in vivo. Dependent on the C5-substituent, the compounds showed high selectivity for MCF-7 cells. Especially 2-oxoethyl benzoate derivatives were inactive at the MDA-MB-231 cell line and as active as 5-FU at MCF-7 cells. C5-acetyl (8a), –2-oxoethyl formiate (8e), –2-oxoethyl acetate (8f) and –2-oxoethyl propionate (8g) derivatives showed growth inhibition at both cell lines, comparable with cisplatin. Modifications significantly reduced the inhibitory potency at COX-1 and COX-2 in vitro and in the xylene-induced ear swelling assay in mice. Only compound 8a was equipotent to licofelone, ibuprofen and celecoxibe in vivo. [Copyright &y& Elsevier]

Here-in, we present molecular design, chemical synthesis and evaluation of novel chromenyl-based 2-iminothiazolidin-4-one derivatives as tubulin polymerization inhibitors. The newly synthesized compounds were evaluated for their in vitro cytotoxicities against A549 (lung cancer), MDA-MB-231 and BT-471 (breast cancer), HepG2 (liver cancer) and HCT-116 (colon cancer) cell lines by MTT assay. Among the synthesized compounds, compound 12b showed excellent anticancer activity on MDA-MB-231 cell line with IC 50 value of 0.95 ± 1.88 μM and was verified to be safe in normal human bronchial epithelial cells (Beas-2B). Apoptosis induced by the lead 12b was observed using morphological observations, AO/EB and DAPI staining procedures. Further, dose-dependent increase in the depolarization of mitochondrial membrane was also observed through JC-1 staining. Annexin V-FITC/PI assay confirmed that 12b induced early apoptosis. Additionally, cell cycle analysis indicated that the MDA-MB-231 cells were arrested at sub-G2/M phase and also inhibited tubulin polymerization with IC 50 value of 3.54 ± 0.2 μM. Molecular docking simulations were employed to identify the important binding modes responsible for the tubulin inhibitory activity, thus supporting their effective anticancer potential. Image 1 • The new chromenyl-based 2-iminothiazolidin-4-one derivatives were synthesized. • Compound 12b induced apoptosis and cell cycle arrest in G2/M phase in MDA-MB-231 cancer cells. • 12b was almost 28-fold more selective on MDA-MB-231 cells compared to Beas-2B cells. • 12b inhibited tubulin polymerization with an IC 50 value of 3.54 ± 0.2 µM. • Binding modes of 12b responsible for tubulin inhibition were identified by molecular docking analysis. [ABSTRACT FROM AUTHOR]