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Isodesmic reactions, in which chemical bonds are redistributed between substrates and products, provide a general and powerful strategy for both biological and chemical synthesis. However, most isodesmic reactions involve either metathesis or functional‐group transfer. Here, we serendipitously discovered a novel isodesmic reaction of indoles and anilines that proceeds intramolecularly under weakly acidic conditions. In this process, the five‐membered ring of the indole motif is broken and a new indole motif is constructed on the aniline side, accompanied by the formation of a new aniline motif. Mechanistic studies revealed the pivotal role of σ→π* hyperconjugation on the nitrogen atom of the indole motif in driving this unusual isodesmic reaction. Furthermore, we successfully synthesized a diverse series of polycyclic indole derivatives; among quinolines, potential antitumor agents were identified using cellular and in vivo experiments, thereby demonstrating the synthetic utility of the developed methodology. [ABSTRACT FROM AUTHOR]

An integrated platform was developed for NP-inspired PROTAC design, target identification and drug discovery. As a proof-of-concept study, this platform was applied to target characterization of 3-fluoro-10-hydroxylevodiamine, which highlighted the superiority of PROTAC technology in target identification of NPs and accelerated the process of NPs-based drug discovery. [Display omitted] • A new strategy combining PROTAC derivatization, quantitative proteomic analysis and binding affinity validation was developed for target identification and drug discovery of natural products. • The PROTAC-based target identitication strategy was successfully applied to characterize REXO4 as a direct target of 3-fluoro-10-hydroxylevodiamine. • Evodiamine-inspired PROTAC 13c showed potent antitumor activity and reduced toxic side effects through REXO4 degradation. Natural products (NPs) play a crucial role in the development of therapeutic drugs. However, it is still highly challenging to identify the targets of NPs. Besides, NPs usually exert their pharmacological activities via acting on multiple targets or pathways, which also poses great difficulties for the target identification of NPs. Inspired by our continuous efforts in designing drug-like protein degraders, this study introduced a successful example for the target identification and drug discovery of natural products evodiamine by employing PROTAC technology. Taking advantages of proteolysis targeting chimera (PROTAC), herein an integrated strategy combining PROTAC derivatization, quantitative proteomic analysis and binding affinity validation was developed for target identification and drug discovery of antitumor NP evodiamine. In this study, both highly potent PROTACs and negative controls were designed for quantitative proteomic analysis. Furthermore, REXO4 was confirmed as a direct target of 3-fluoro-10-hydroxylevodiamine, which induced cell death through ROS. In addition, the PROTAC 13c effectively degraded REXO4 both in vitro and in vivo , leading to potent antitumor activities and reduced toxic side effects. In summary, we developed an integrated strategy for the target identification and drug discovery of NPs, which was successfully applied to the PROTAC derivatization and target characterization of evodiamine. This proof-of-concept study highlighted the superiority of PROTAC technology in target identification of NPs and accelerated the process of NPs-based drug discovery, exhibiting broad application in NP-based drug development. [ABSTRACT FROM AUTHOR]

Introduction: Natural products (NPs) play a crucial role in the development of therapeutic drugs. However, it is still highly challenging to identify the targets of NPs. Besides, NPs usually exert their pharmacological activities via acting on multiple targets or pathways, which also poses great difficulties for the target identification of NPs. Objectives: Inspired by our continuous efforts in designing drug-like protein degraders, this study introduced a successful example for the target identification and drug discovery of natural products evodiamine by employing PROTAC technology. Methods: Taking advantages of proteolysis targeting chimera (PROTAC), herein an integrated strategy combining PROTAC derivatization, quantitative proteomic analysis and binding affinity validation was developed for target identification and drug discovery of antitumor NP evodiamine. Results: In this study, both highly potent PROTACs and negative controls were designed for quantitative proteomic analysis. Furthermore, REXO4 was confirmed as a direct target of 3-fluoro-10-hydroxylevodiamine, which induced cell death through ROS. In addition, the PROTAC 13c effectively degraded REXO4 both in vitro and in vivo, leading to potent antitumor activities and reduced toxic side effects. Conclusion: In summary, we developed an integrated strategy for the target identification and drug discovery of NPs, which was successfully applied to the PROTAC derivatization and target characterization of evodiamine. This proof-of-concept study highlighted the superiority of PROTAC technology in target identification of NPs and accelerated the process of NPs-based drug discovery, exhibiting broad application in NP-based drug development.

Comprehensive Summary: Twelve new limonoids (1—12), named trichilitins A—L, were isolated from the leaves and twigs of Trichilia connaroides, together with ten known compounds (13—22). The structures were elucidated by extensive spectroscopic investigations, X‐ray diffraction analyses, and ECD calculations. Compound 1, which belongs to a unique class of ring B‐seco limonoid, has been identified as 6/7/6/5 tetracyclic due to a key Baeyer‐Villiger oxidation. Compounds 2—7 were identified as ring intact limonoids, while compounds 8—10 were established as ring D‐seco ones, and 11 and 12 were determined to be rearranged ones. All of the compounds were tested for cytotoxicity against three human tumor cell lines (HCT‐116, NCl‐H1975, and SH‐SY5Y). Compounds 6, 7, 13, 14, and 19 exhibited significant cytotoxic effects, especially 7 exhibited significant cytotoxic effects against HCT‐116 with an IC50 value of 0.035 μmol·L–1 and was more active than the positive control, doxorubicin with an IC50 value of 0.20 μmol·L–1. Compound 7 effectively induced apoptosis of HCT‐116, which was associated with S‐phase cell cycle arrest. Furthermore, the Western blot analysis showed that compound 7 could induce cell cycle arrest by promoting the expression levels of p53 and p21. [ABSTRACT FROM AUTHOR]

The use of bevacizumab has been hampered by safety concerns despite demonstrable progression-free survival (PFS) benefit in subjects with platinum-resistant ovarian cancer, highlighting the need for novel effective and safe antiangiogenic agents. This study aimed to characterize the tolerability, safety, and antitumor activities of escalating doses of anti-VEGF antibody suvemcitug plus chemotherapy in platinum-resistant ovarian cancer patients. This open-label, dose-escalation trial enrolled adult patients (≥18 years) with platinum-resistant histologically or cytologically-confirmed epithelial ovarian, fallopian tube and primary peritoneal cancer. Eligible patients received paclitaxel or topotecan plus escalating doses of suvemcitug 0.5, 1, 1.5, or 2 mg/kg once every two weeks. The primary endpoints were safety and tolerability, and antitumor activities of suvemcitug. Twenty-nine subjects received paclitaxel (n = 11) or topotecan (n = 18). No dose-limiting toxicities occurred. The most common adverse events of special interest were proteinuria (41.4%), hypertension (20.7%) and epistaxis (10.3%). No gastrointestinal perforations occurred. Nine subjects (31.0%, 95% CI 15.3–50.8) demonstrated investigators-confirmed objective response, including complete response in 1 and partial response in 8. The median PFS was 5.4 months (95% CI 2.2–7.4). Suvemcitug demonstrated an acceptable safety profile and promising antitumor activities in platinum-resistant ovarian cancer patients, supporting its further clinical development. • In this trial, 29 platinum-resistant ovarian cancer patients received escalating doses of suvemcitug plus chemotherapy. • No dose-limiting toxicities occurred and no gastrointestinal perforations were reported. • Nine patients showed investigators-confirmed objective response, with a median progression-free survival of 5.4 months. • The recommended dose for phase 2 study is suvemcitug 1.5 mg/kg every two weeks. • The safety and antitumor activities of suvemcitug support its clinical development for platinum-resistant ovarian cancer. [ABSTRACT FROM AUTHOR]

Using a diazonium combination of aniline and 1,3‐diphenylpropane‐1,3‐dione, the Japp‐Klingemann reaction yielded the 1,3‐diphenyl‐2‐(2‐phenylhydrazono)propane‐1,3‐dione ligand (HL). The copper (II) complex has been made using copper (II) acetate salt. The geometry of HL and its Cu (II) chelate were described through CHN analyses, FTIR, UV–Visible, XRD, TGA, and magnetic susceptibility tests. According to the spectral data, the ligand exhibits monobasic bidentate behavior by connecting through the N atom of hydrazone moiety (=N − NH−) by deprotonating beside the oxygen atom of the carbonyl (C=O) group forming octahedral geometry. Density functional theory (DFT) calculations were done by molecular studio software to examine the optimal geometry of HL and its complexity. MCF‐7 and HepG‐2 cell lines demonstrated anticancer action in response to the HL and its copper (II) complex. Additionally, inhibition zone diameter was used to assess the in vitro antibacterial action of HL and particular complex toward Gram +ve bacteria Staphylococcus aureus and Gram‐ve bacteria Escherichia coli (E. coli). Both viscosity and absorption spectra of Calf‐thymus DNA binding experimentations were used to examine the compounds. [ABSTRACT FROM AUTHOR]

[Mn(SCN)2(2,2′-bipy)2] (1) and [Co(SCN)2(2,2′-bipy)2] (2) were synthesized at ambient temperature by adding aqueous solutions of manganese(II) or cobalt(II) chloride hydrate to aqueous acetonitrile solutions of 2,2′-bipyridine (2,2′-bipy) and potassium thiocyanate. Elemental analyses, FT-IR and UV–vis spectra were used to characterize 1 and 2. Single crystal X-ray diffraction was used to analyze the crystal structures of 1 and 2, revealing that the two are structurally similar. The molecular structures of 1 and 2 consist of Mn or Co ion chelated by two molecules of 2,2′-bipy through four nitrogen atoms and two NCS anions, giving distorted octahedral geometries. The isothiocyanate group is not bridging, instead, two ligands coordinate in a cis arrangement to the manganese or cobalt center by their nitrogen atoms while the sulfur atoms are free. Through hydrogen bonding and π–π stacking interactions, the discrete units of 1 and 2 extend to 3D supramolecular networks with flower and fishbone-like structures. The luminescence behavior of 2,2′-bipy, 1 and 2 were investigated. On HepG2 (liver) and MCF-7 (breast) cancer cells, the anticancer effects of 1 and 2 were evaluated. The activity of 1 and 2 on MCF-7 is more significant than that of HepG2. The IC50 of 1 was lower in HepG2 and MCF-7 cells than for 2. [ABSTRACT FROM AUTHOR]

Background: Breast cancer poses a major threat to female health worldwide. One of the medicinal plants used in traditional Saudi medicine is the Juniperus procera (Arar) plant, which is used to cure various illnesses, including cancer. Objectives: The cytotoxic properties of Saudi J. procera extracts and their regulatory mechanisms against tumorigenesis in breast cancer were investigated. Methods: The antioxidant capacities of the fruit and leaf extracts were detected by the 2,2'-azino-bis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assay and 2,2-diphenyl-1-1picrylhydrazyl (DPPH) assay. The cell viability of the extracts was determined by 3-(4,5-dimethylthiazoyl)-2,5-diphenyl-tetrazolium bromide assay. The cell migration was detected by a wound healing assay. The cell cycle and cell apoptosis were analyzed by flow cytometry. The reactive oxygen species (ROS) was evaluated using a DCFDA-cellular (the cell permeant reagent 2',7' -dichlorofluorescein diacetate) reactive oxygen species detection assay. The protein and gene expression levels were estimated by western blotting and Reverse transcription polymerase chain reaction (RTPCR), respectively. Results: Phytochemical analysis revealed a high content of phenolic and flavonoids in fruit and leaf extracts. Relative to leaf extract, the fruit extract showed higher antioxidant activities and exhibited more potent cytotoxic effects against two breast cancer cell lines: MCF-7 and MDA-MB-231. The fruit extract arrested the cell cycle of the tested cancer cell lines in S phase and G1 phase, and downregulated PI3K (phosphoinositide 3-kinase-protein kinase)/Akt (protein kinase B)/mTOR (Mammalian target of rapamycin) pathway. It also suppressed aromatase expression in MCF-7 but upregulated it in MDA-MB-231. Conclusion: J procera fruit and leaf extracts have significant antitumor activities against MCF-7 and MDA-MB-231 breast cancer cell lines. [ABSTRACT FROM AUTHOR]

The clinically approved human epidermal growth factor receptor 2 (HER2)-targeting monoclonal antibodies (mAbs), trastuzumab, and pertuzumab, target domains IV and II, respectively. Trastuzumab is now the standard treatment for HER2-overexpressed breast and gastric cancers, and trastuzumab in combination with pertuzumab showed clinical benefit. However, there still exist patients who do not respond to the therapy. Furthermore, HER2 mutants that cannot be recognized by pertuzumab were found in tumors. Therefore, novel anti-HER2 mAbs and modalities have been desired. In our previous study, we developed a novel anti-HER2 domain I mAb, H2Mab-139 (mouse IgG1, kappa). We herein produced a defucosylated mouse IgG2a type of mAb against HER2 (H2Mab-139-mG2a-f) to enhance antibody-dependent cellular cytotoxicity (ADCC)-mediated antitumor activity. H2Mab-139-mG2a-f exhibits a high binding affinity in flow cytometry with the dissociation constant (KD) determined to be 3.9 × 10−9 M and 7.7 × 10−9 M against HER2-overexpressed Chinese hamster ovary (CHO)-K1 (CHO/HER2) and HER2-positive BT-474 cells, respectively. Moreover, we showed that H2Mab-139-mG2a-f exerted ADCC and complement-dependent cytotoxicity against CHO/HER2 and BT-474 in vitro and exhibited potent antitumor activities in mouse xenograft models. These results indicated that H2Mab-139-mG2a-f exerts antitumor effects against HER2-positive human breast cancers and is useful as an antibody treatment for HER2-positive human cancers.

Carboxymethyl pachymaran (CMP) was treated via high-temperature and cellulase hydrolysis to obtain HTCMP, HTEC-24, and HTEC-48. The chemical structure and in vivo antitumor activities of the four types of CMPs were investigated. Compared with CMP (787.9 kDa), the molecular weights of HTCMP, HTEC-24, and HTEC-48 were decreased to 429.8, 129.9, and 68.6 kDa, respectively. The viscosities and particle sizes of the CMPs could also decrease with the decline in the molecular weights. All the CMPs showed antitumor abilities, but HTEC-24 exhibited the best activity. In the animal study, when curing the spleen and thymus, CMPs displayed immunomodulatory effects by increasing the secretion of IFN-γ and IL2 in mice. The CMPs also exerted an antitumor ability by regulating the gut microbiota in tumor-bearing mice. Our results established a foundation to develop an antitumor drug with CMP. [ABSTRACT FROM AUTHOR]

A series of novel derivatives of 18β-glycyrrhetinic acid (GA) were synthesized by introducing aromatic or heterocyclic structures to extend the side chain, thereby enhancing their interaction with amino acid residues in the active pocket of the target protein. These compounds were structurally characterized using 1H NMR, 13C NMR, and HRMS. The compounds were subsequently evaluated for their inhibitory effects on HIV-1 protease and cell viability in the human cancer cell lines K562 and HeLa and the mouse cancer cell line CT26. Towards HIV-1 protease, compounds 28 and 32, which featured the introduction of heterocyclic moieties at the C3 position of GA, exhibited the highest inhibition, with inhibition rates of 76% and 70.5%, respectively, at 1 mg/mL concentration. Further molecular docking suggests that a 3-substituted polar moiety would be likely to enhance the inhibitory activity against HIV-1 protease. As for the anti-proliferative activities of the GA derivatives, incorporation of a thiazole heterocycle at the C3- position in compound 29 significantly enhanced the effect against K562 cells with an IC50 value of 8.86 ± 0.93 µM. The introduction of electron-withdrawing substituents on the C3-substituted phenyl ring augmented the anti-proliferative activity against Hela and CT26 cells. Compound 13 exhibited the highest inhibitory activity against Hela cells with an IC50 value of 9.89 ± 0.86 µM, whereas compound 7 exerted the strongest inhibition against CT26 cells with an IC50 value of 4.54 ± 0.37 µM. These findings suggest that further modification of GA is a promising path for developing potent novel anti-HIV and anticancer therapeutics. [ABSTRACT FROM AUTHOR]

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The Janus kinase/signal transducer and activator of the transcription 3 (JAK/STAT3) signaling pathway controls multiple biological processes, including cell survival, proliferation, and differentiation. Abnormally activated STAT3 signaling promotes tumor cell growth, proliferation, and survival, as well as tumor invasion, angiogenesis, and immunosuppression. Hence, JAK/STAT3 signaling has been considered a promising target for antitumor therapy. In this study, a number of ageladine A derivative compounds were synthesized. The most effective of these was found to be compound 25. Our results indicated that compound 25 had the greatest inhibitory effect on the STAT3 luciferase gene reporter. Molecular docking results showed that compound 25 could dock into the STAT3 SH2 structural domain. Western blot assays demonstrated that compound 25 selectively inhibited the phosphorylation of STAT3 on the Tyr705 residue, thereby reducing STAT3 downstream gene expression without affecting the expression of the upstream proteins, p-STAT1 and p-STAT5. Compound 25 also suppressed the proliferation and migration of A549 and DU145 cells. Finally, in vivo research revealed that 10 mg/kg of compound 25 effectively inhibited the growth of A549 xenograft tumors with persistent STAT3 activation without causing significant weight loss. These results clearly indicate that compound 25 could be a potential antitumor agent by inhibiting STAT3 activation. [ABSTRACT FROM AUTHOR]

Schiff bases ligand (HL) was produced by condensing 4-aminobenzohydrazide with N-(4-chlorophenyl)-2-(4-formylphenoxy)acetamide. Cobalt (II), nickel (II), and copper (II) acetate and ligand are reacted to form 1:1 complexes. By using electronic spectra, magnetic susceptibility measurements, infrared data from 1H NMR, and XRD studies, the ligand and its metal complexes have been characterized. According to the spectrum data, the ligand functions as a monobasic bidentate, coordinating with the nitrogen atom of azomethine (−CN−) group and the oxygen atom of carbonyl group in enol form. An octahedral structure has been proposed for Co(II), Ni(II), and Cu(II) complexes according to magnetic and electronic spectrum analysis. Using the DFT method, the computational investigations of the ligand and its metal complexes showed the bond lengths, bond angles, and quantum chemical parameters. To determine the thermal stability and mode of thermal degradation of hydrazone ligand and its complexes, thermogravimetric analysis was approved out on the samples. Two calculated method, Horowitz-Metzger and Coats-Redfern, were used to calculate the characteristics of the composites' thermal degradation mechanisms at each step, including their breakdown kinetics. The ligand and its complexes were investigated for their cytotoxicity in vitro compared to human amnion (WISH) and epitheliod carcinoma (Hela). The Ni(II) complex showed highly inhibition against (WISH) growth (IC50 = 18.28±1.8 μM) with relationship to the produced chemicals and other common medications. The interaction between the ligand and its complexes with the genetic tumor (3hb5) receptor was examined using docking experiments.

The epithelial cell adhesion molecule (EpCAM) is a stem cell and carcinoma antigen, which mediates cellular adhesion and proliferative signaling by the proteolytic cleavage. In contrast to low expression in normal epithelium, EpCAM is frequently overexpressed in various carcinomas, which correlates with poor prognosis. Therefore, EpCAM has been considered as a promising target for tumor diagnosis and therapy. Using the Cell-Based Immunization and Screening (CBIS) method, we previously established an anti-EpCAM monoclonal antibody (EpMab-37; mouse IgG1, kappa). In this study, we investigated the antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and an antitumor activity by a defucosylated mouse IgG2a-type of EpMab-37 (EpMab-37-mG2a-f) against a breast cancer cell line (BT-474) and a pancreatic cancer cell line (Capan-2), both of which express EpCAM. EpMab-37-mG2a-f recognized BT-474 and Capan-2 cells with a moderate binding-affinity [apparent dissociation constant (KD): 2.9 × 10−8 M and 1.8 × 10−8 M, respectively] by flow cytometry. EpMab-37-mG2a-f exhibited ADCC and CDC for both cells by murine splenocytes and complements, respectively. Furthermore, administration of EpMab-37-mG2a-f significantly suppressed the xenograft tumor development compared with the control mouse IgG. These results indicated that EpMab-37-mG2a-f exerts antitumor activities and could provide valuable therapeutic regimen for breast and pancreatic cancers. [ABSTRACT FROM AUTHOR]

Carboxymethyl pachymaran (CMP) was treated via high-temperature and cellulase hydrolysis to obtain HTCMP, HTEC-24, and HTEC-48. The chemical structure and in vivo antitumor activities of the four types of CMPs were investigated. Compared with CMP (787.9 kDa), the molecular weights of HTCMP, HTEC-24, and HTEC-48 were decreased to 429.8, 129.9, and 68.6 kDa, respectively. The viscosities and particle sizes of the CMPs could also decrease with the decline in the molecular weights. All the CMPs showed antitumor abilities, but HTEC-24 exhibited the best activity. In the animal study, when curing the spleen and thymus, CMPs displayed immunomodulatory effects by increasing the secretion of IFN-γ and IL2 in mice. The CMPs also exerted an antitumor ability by regulating the gut microbiota in tumor-bearing mice. Our results established a foundation to develop an antitumor drug with CMP.

A series of novel derivatives of 18β-glycyrrhetinic acid (GA) were synthesized by introducing aromatic or heterocyclic structures to extend the side chain, thereby enhancing their interaction with amino acid residues in the active pocket of the target protein. These compounds were structurally characterized using 1H NMR, 13C NMR, and HRMS. The compounds were subsequently evaluated for their inhibitory effects on HIV-1 protease and cell viability in the human cancer cell lines K562 and HeLa and the mouse cancer cell line CT26. Towards HIV-1 protease, compounds 28 and 32, which featured the introduction of heterocyclic moieties at the C3 position of GA, exhibited the highest inhibition, with inhibition rates of 76% and 70.5%, respectively, at 1 mg/mL concentration. Further molecular docking suggests that a 3-substituted polar moiety would be likely to enhance the inhibitory activity against HIV-1 protease. As for the anti-proliferative activities of the GA derivatives, incorporation of a thiazole heterocycle at the C3- position in compound 29 significantly enhanced the effect against K562 cells with an IC50 value of 8.86 ± 0.93 µM. The introduction of electron-withdrawing substituents on the C3-substituted phenyl ring augmented the anti-proliferative activity against Hela and CT26 cells. Compound 13 exhibited the highest inhibitory activity against Hela cells with an IC50 value of 9.89 ± 0.86 µM, whereas compound 7 exerted the strongest inhibition against CT26 cells with an IC50 value of 4.54 ± 0.37 µM. These findings suggest that further modification of GA is a promising path for developing potent novel anti-HIV and anticancer therapeutics.

The antitumor effects of Lycium ruthenicum Murr. polysaccharides (LRPS) and Lycium ruthenicum Murr. anthocyanins (LRAC) were comprehensively investigated in this study. LPRS was obtained by water extraction and alcohol precipitation and further purified using diethylaminoethyl cellulose (DEAE‐Cellulose) and Sephadex G‐75 columns. High‐performance liquid chromatography (HPLC) and Fourier transform‐infrared (FT‐IR) spectroscopy were used to characterize the purified LRPS. The results showed that the purified LRPS contained heteropolysaccharides, mainly composed of arabinose, galactose, and glucose with weight percentage of 41.2%, 33.6%, and 10.8%, respectively. More importantly, LRPS (500 μg/ml) and LRAC (80 μg/ml) failed to impede the proliferation of tumor cells when applied solely (48 h incubation), yet remarkable antineoplastic effects were found once they were applied altogether, since the LoVo cells, a typical human colorectal carcinoma cell line, were significantly inhibited by the mixture of LRPS (150 μg/ml) and LRAC (20 μg/ml) (LRPS&AC) in 24 h. The antineoplastic activity resulted from the combination of both LRPS and LRAC (LRPS&AC), by means of blocking the cell cycle at the G0–G1 phase and inducing LoVo cell apoptosis via reactive oxygen species (ROS)‐dependent pathway. The inhibitory effects of LRPS&AC were specific to the tumor cells, without imposing on the proliferation of normal cells. Western blotting revealed that the antitumor effect was related to the mitochondria‐mediated apoptosis launched by the cross‐action of PI3K/Akt (phosphatidylinositol 3‐kinase/protein kinase B) and JAK2/STAT3 (janus kinase 2/signal transduction and activator of transcription 3) signaling pathways. These findings for the first time reveal the synergistic antitumor effects of LRPS&AC and the related mechanisms, which enable Lycium ruthenicum Murr. to serve as a natural source to develop therapeutic reagents and functional foods with antineoplastic properties. [ABSTRACT FROM AUTHOR]

As rare-earth coordination polymers (CPs) have appreciable antimicrobial properties, ternary lanthanum CPs have been widely synthesized and investigated in recent years. Here, we report convenient, solvent-free reactions between the lanthanum salt and two ligands at mild temperatures that form ternary lanthanum nanoscale CPs with 10-gram-scale. The structural features and morphologies were characterized using a scanning electron microscope (SEM), Fourier transform infrared spectrometer (FT-IR), ultraviolet-visible (UV–Vis), X-ray diffractometer (XRD), X-ray Photoelectron Spectroscopy (XPS), Brunauer–Emmett–Teller (BET), elemental analysis, inductively coupled plasma mass spectrometry (ICP-MS), electrospray ionization mass spectrometry (ESI-MS), nuclear magnetic resonance (NMR), dynamic light scattering (DLS) and analyzer, and thermogravimetric and differential thermal analyzer (TG-DTA). Furthermore, the in vitro antibacterial activities of these ternary hybrids were studied using the zone of inhibition (ZOI) method, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and transmission electron microscope (TEM) and were found to have excellent antibacterial properties. The in vitro antitumor activities were performed in determining the absorbance values by CCK-8 (Cell Counting Kit-8) assay. This facile synthetic method would potentially enable the mass production of ternary lanthanum CPs at room temperature, which can be promising candidates as antibacterial compounds and antitumor agents.

The Janus kinase/signal transducer and activator of the transcription 3 (JAK/STAT3) signaling pathway controls multiple biological processes, including cell survival, proliferation, and differentiation. Abnormally activated STAT3 signaling promotes tumor cell growth, proliferation, and survival, as well as tumor invasion, angiogenesis, and immunosuppression. Hence, JAK/STAT3 signaling has been considered a promising target for antitumor therapy. In this study, a number of ageladine A derivative compounds were synthesized. The most effective of these was found to be compound 25. Our results indicated that compound 25 had the greatest inhibitory effect on the STAT3 luciferase gene reporter. Molecular docking results showed that compound 25 could dock into the STAT3 SH2 structural domain. Western blot assays demonstrated that compound 25 selectively inhibited the phosphorylation of STAT3 on the Tyr705 residue, thereby reducing STAT3 downstream gene expression without affecting the expression of the upstream proteins, p-STAT1 and p-STAT5. Compound 25 also suppressed the proliferation and migration of A549 and DU145 cells. Finally, in vivo research revealed that 10 mg/kg of compound 25 effectively inhibited the growth of A549 xenograft tumors with persistent STAT3 activation without causing significant weight loss. These results clearly indicate that compound 25 could be a potential antitumor agent by inhibiting STAT3 activation.

A new Ag(I) coordination complex, Ag(C11H10N2O)2·NO3 (C11H10N2O = 4-(2-hydroxyphenyl)-2-methylpyrimidine) is successfully synthesized and characterized by infrared spectroscopy, elemental analysis, and single-crystal X-ray diffraction analysis. This complex features a three-dimensional framework consisting of hydrogen bonds, π–π stacking interactions, coordination interactions, and electrostatic interactions. Moreover, the thermal stability and non-isothermal thermal decomposition reaction kinetics of the complex are well investigated by the methods of Kissinger and Ozawa. Finally, the antitumor ability of the complex is evaluated against human lung cancer cells (NCI-H460), human hepatocellular cancer cells (HepG2), and human breast cancer cells (MCF7). The complex exhibits potent antitumor activities against HepG2 and MCF7 cancer cells. [ABSTRACT FROM AUTHOR]

A new diterpenoid, namely millipedine A (10), along with nine known compounds (1-9), were isolated from the methanol extract of Millipede. Their structures were established on the basis of spectroscopic analysis including one and two-dimensional NMR spectroscopy and comparison with previously reported data. New compound showed moderate cytotoxicity against A549, HCT-116, and SW1990 cell lines in MTT assay. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a common malignant tumour of human digestive tract. The high mortality rate of CRC is closely related to the limitations of existing treatments. Thus, there is an urgent need to search for new anti-CRC agents. In this work, twenty novel coumarin-dithiocarbamate derivatives (IDs) were designed, synthesized and evaluated in vitro. The results suggest that the most active compound ID-11 effectively inhibited the proliferation of CRC cell lines while shown little impact on normal colon epithelial cells. Mechanism studies revealed that ID-11 displayed bromodomain-containing protein 4 inhibitory activity, and induced G2/M phase arrest, apoptosis as well as decreased the expression levels of the key genes such as c-Myc and Bcl-2 in CRC cell lines. Moreover, the ADMET properties prediction results shown that ID-11 possess well metabolic characteristics without obvious toxicities. Our data demonstrated that compound ID-11 may be a promising anti-CRC agent and deserved for further development.

Colorectal cancer (CRC) is a common malignant tumour of human digestive tract. The high mortality rate of CRC is closely related to the limitations of existing treatments. Thus, there is an urgent need to search for new anti-CRC agents. In this work, twenty novel coumarin-dithiocarbamate derivatives (IDs) were designed, synthesized and evaluated in vitro. The results suggest that the most active compound ID-11 effectively inhibited the proliferation of CRC cell lines while shown little impact on normal colon epithelial cells. Mechanism studies revealed that ID-11 displayed bromodomain-containing protein 4 inhibitory activity, and induced G2/M phase arrest, apoptosis as well as decreased the expression levels of the key genes such as c-Myc and Bcl-2 in CRC cell lines. Moreover, the ADMET properties prediction results shown that ID-11 possess well metabolic characteristics without obvious toxicities. Our data demonstrated that compound ID-11 may be a promising anti-CRC agent and deserved for further development. [ABSTRACT FROM AUTHOR]

Chemo-photodynamic therapy is a treatment method that combines chemotherapy and photodynamic therapy and has demonstrated significant potential in cancer treatment. However, the development of chemo-photodynamic therapeutic agents with fewer side effects still poses a challenge. Herein, we designed and synthesized a novel series of β-carboline/furylmalononitrile hybrids 10a - i and evaluated their chemo-photodynamic therapeutic effects. Most of the compounds were photodynamically active and exhibited cytotoxic effects in four cancer cells. In particular, 10f possessed type-I/II photodynamic characteristics, and its 1 O 2 quantum yield increased by 3-fold from pH 7.4 to 4.5. Most interestingly, 10f exhibited robust antiproliferative effects by tumor-selective cytotoxicities and hypoxic-overcoming phototoxicities. In addition, 10f generated intracellular ROS and induced hepatocellular apoptosis, mitochondrial damage, and autophagy. Finally, 10f demonstrated extremely low acute toxicity (LD 50 = 1415 mg/kg) and a high tumor-inhibitory rate of 80.5% through chemo-photodynamic dual therapy. Our findings may provide a promising framework for the design of new photosensitizers for chemo-photodynamic therapy.

A new fatty acid-spirostan steroid glycoside ester, a new cholestane glycoside and a new stilbene trimer, along with three known steroidal saponins, were isolated from the 70% EtOH extract of the roots and rhizomes of Trillium tschonoskii Maxim. The structure of isolated compounds was elucidated by spectroscopic analysis. Compound 1–6 were assessed for their cytotoxicity against cancer cell lines (MCF-7, HCT-116, DU-145, SGC-7901, MCF-7/ADR, K562/ADR), and the result showed that compound 4 was highly toxic to six human tumor cell lines. [ABSTRACT FROM AUTHOR]

The epithelial cell adhesion molecule (EpCAM) is a stem cell and carcinoma antigen, which mediates cellular adhesion and proliferative signaling by the proteolytic cleavage. In contrast to low expression in normal epithelium, EpCAM is frequently overexpressed in various carcinomas, which correlates with poor prognosis. Therefore, EpCAM has been considered as a promising target for tumor diagnosis and therapy. Using the Cell-Based Immunization and Screening (CBIS) method, we previously established an anti-EpCAM monoclonal antibody (EpMab-37; mouse IgG1, kappa). In this study, we investigated the antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and an antitumor activity by a defucosylated mouse IgG2a-type of EpMab-37 (EpMab-37-mG2a-f) against a breast cancer cell line (BT-474) and a pancreatic cancer cell line (Capan-2), both of which express EpCAM. EpMab-37-mG2a-f recognized BT-474 and Capan-2 cells with a moderate binding-affinity [apparent dissociation constant (KD): 2.9 × 10−8 M and 1.8 × 10−8 M, respectively] by flow cytometry. EpMab-37-mG2a-f exhibited ADCC and CDC for both cells by murine splenocytes and complements, respectively. Furthermore, administration of EpMab-37-mG2a-f significantly suppressed the xenograft tumor development compared with the control mouse IgG. These results indicated that EpMab-37-mG2a-f exerts antitumor activities and could provide valuable therapeutic regimen for breast and pancreatic cancers.

Featured Application: Vegetable oils are a rich source of fatty acids and bioactive compounds with numerous beneficial effects to human health. The presented results showed that seed oils of linseed, purslane, luffa, and pumpkin have significant antimicrobial properties that could find application in the food industry as functional ingredients or as non-synthetic antimicrobial agents in the design of new healthy food products. Moreover, they could be used in mixtures with other oils to design new vegetable oils with functional properties and enhance content in omega-3 fatty acids. In the present study, the antimicrobial and cytotoxic activities, as well as the fatty acids composition in vegetable seed oils from linseed, purslane, luffa, and pumpkin were evaluated. For this purpose, two linseed oils and one luffa oil were commercially obtained, while purslane and pumpkin oils were obtained from own cultivated seeds. The results showed a variable fatty acids composition among the tested oils, with α-linolenic, linoleic, oleic, palmitic, and stearic acid being the most abundant compounds. In regards to particular oils, linseed oils were a rich source of α-linolenic acid, luffa and pumpkin oil were abundant in linoleic acid, while purslane oil presented a balanced composition with an almost similar amount of both fatty acids. Luffa oil was the most effective against two of the tested cancer cell lines, namely HeLa (cervical carcinoma) and NCI-H460 (non-small cell lung cancer), while it also showed moderate toxicity against non-tumor cells (PLP2 cell line). Regarding the antibacterial activity, linseed oil 3 and pumpkin oil showed the highest activity against most of the tested bacteria (especially against Enterobacter cloacae and Escherichia coli) with MIC and MBC values similar to the used positive controls (E211 and E224). All the tested oils showed significant antifungal activities, especially luffa and pumpkin oil, and for most of the tested fungi they were more effective than the positive controls, as for example in the case of Aspergillus versicolor, A. niger, and Penicillium verrucosum var. cyclopium. In conclusion, the results of our study showed promising antimicrobial and cytotoxic properties for the studied seed oils which could be partly attributed to their fatty acids composition, especially the long-chain ones with 12–18 carbons. [ABSTRACT FROM AUTHOR]

Panax ginseng, an ancient herb, belonging to Chinese traditional medicine, is an important herb that has a remarkable impact on various diseases. Ginsenoside Rg3, one of the most abundant ginsenosides, exerts significant functions in the prevention of various types of cancers with few side effects. In the present review, its functional molecular mechanisms are explored, including the improvement of antioxidant and anti-inflammation properties, immune regulation, induction of tumor apoptosis, prevention of tumor invasion and metastasis, tumor proliferation and angiogenesis, and reduction of chemoresistance and radioresistance. On the other hand, metabolism, pharmacokinetics and clinical indications of Rg3 are also discussed. The biological functional role of ginsenoside Rg3 may be associated with that it is a steroid glycoside with diverse biological activities and many signaling pathway can be regulated. Many clinical trials are highly needed to confirm the functions of ginsenoside Rg3. [ABSTRACT FROM AUTHOR]

Juglans mandshurica Maxim., also known as “Manchurian walnut” (Chinese) and “Onigurumi” (Japanese), is a medicinal plant widely distributed in Western and Central Asia, especially in China. It has been traditionally used to treat cancer, gastric ulcers, diarrhea, dysentery, dermatosis, uterine prolapse, and leukopenia. To date, more than 400 constituents including quinones (e.g. naphthoquinones, anthraquinones, naphthalenones, tetralones), phenolics, flavonoids, triterpenoids, coumarins, lignans, phenylpropanoids, diarylheptanoids, and steroids, were isolated and structurally identified from different plant parts of J. mandshurica. Among them, quinones, phenolics, triterpenoids, and diarylheptanoids, as the major bioactive substances, have been extensively studied and displayed significant bioactivity. Previous studies have demonstrated that J. mandshurica and a few of its active components exhibit a wide range of pharmacologically important properties, such as antitumor, immunomodulatory, anti-inflammatory, neuroprotective, anti-diabetic, antiviral, antimicrobial, and anti-melanogenesis activities. However, many investigations on biological activities were mainly based on crude extracts of this plant, and the major bioactive ingredients responsible for these bioactivities have not been well identified. Further in vitro and in vivo studies on the mechanisms of action of the pure bioactive compounds, and more elaborate toxicity studies as well as clinical studies are needed to ensure safety and effectiveness of the plant for human use. Taken together, the present review will provide some specific useful suggestions guide to further investigations and applications of this plant in the preparation of medicines and functional foods.

In order to screen endophytic bacteria resources with antitumor activities from medicinal plant, 300 endophytic actinomycetes isolated from Dracaena cochinchinensis collected from Xishuangbanna, China and Vietnam 'were studied. SRB method wras used to detect the activity of antitumor cells, agar diffusion and plate confrontation methods ■were used to test antimicrobial activities, Polymerase Chain Reaction wras used to detect NRPS, PKS-1 and PKS-D genes, and the taxonomic studies of the five selected active strains wrere performed using 16S rRNA gene analysis. Eight media wrere designed to cultivate five selected active strains and the antimicrobial activities of their fermented extraction ■were detected by oxford-cup test against ten pathogenic bacteria and three pathogenic fungi, the antitumor activities 'were measured by MIT assay in twro tumor cell lines. As a result, four of the five active strains wrere classified as Streptomyces spp. and the remaining one as Nocardioides sp. Different media resulted in different activities, most media of strain S04 sho\wed strong activities against eight pathogens and the inhibition rate of the fermentation product of S04 in Medium C on Hep G2 cell line 'was up to 100% , 'which could be a novel resource for the mining of bioactive compounds for further studies. [ABSTRACT FROM AUTHOR]

An efficient and practical reductive rearrangement reaction has been developed for the stereoselective synthesis of diverse piperidinones. This transformation features mild conditions, good substrate/functional group compatibility and large‐scale synthetic potential. Subsequent combined DFT and experimental studies revealed a reduction triggered cascade pathway in which the active imine species was involved as the key intermediate. The biological application of the products has also been demonstrated by acting as the potent antitumor agents, which further strengthens the synthetic utility of this approach. [ABSTRACT FROM AUTHOR]

Grifola frondosa is a basidiomycete fungus with potential biomedical applications owing to the presence of bioactive polysaccharides. The activities of polysaccharides are influenced by many factors, particularly temperature; however, the optimal temperature and conditions for preparation of polysaccharides from this organism have not yet been determined. Therefore, in this study, cold-water soluble polysaccharides from Grifola frondosa were extracted at 4 °C (GFP-4) and purified. GFP-4-30, GFP-4-60 and GFP-4-90 were obtained from GFP-4 after treatment at 30 °C, 60 °C, or 90 °C, respectively, for 6 h. MTT results showed that GFP-4 had the highest inhibitory effects on the proliferation of SPC-A-1 cells in vitro. High-performance gel permeation chromatography results demonstrated that the molecular weight of GFP-4 was 1.05 × 106 Da and that GFP-4-30, GFP-4-60, and GFP-4-90 showed different levels of degradation and generated small molecule sugars. Fourier transform infrared spectroscopy, gas chromatography, and nuclear magnetic resonance results indicated that GFPs mainly consisted of α-d-Galp, α-d-Manp and α-d-Glcp. Periodate oxidation, Smith degradation, and methylation results showed that the backbones of the molecules consisted of 1,3-linked-Galp. After heat treatment, percentages of (1 → 3,4) α-d-Galp in heat-treated polysaccharides were obviously decreased, indicating their lower branching degree, and resulting in weaker antitumor effects. Overall, our findings demonstrated changes in the structure-activity relationships of GFP-4 after heat treatment and provided a theoretical basis for the application of GFP-4 in the food and drug industries. [ABSTRACT FROM AUTHOR]

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In this work, a native exopolysaccharide (nEPS) produced by Halomonas desertis G11 isolated from a Tunisian extreme environment was modified by gamma irradiation. Characterization as well as the antioxidant and antitumor activities of nEPS and its gamma-irradiated derivatives (iEPSs) were comparatively evaluated. In vitro and in vivo antioxidant potentials were determined by using different methods and through different antioxidant enzymes. The antitumor activity was checked against a human colon cancer cell line. Analyses of the complete genome sequence were carried out to identify genes implicated in the production of nEPS. Thus, the genomic biosynthesis pathway and the export mechanism of nEPS were proposed. Analyses of irradiation data showed that iEPSs acquired new functional groups, lower molecular weights, and gained significantly (p < 0.05) higher antioxidant and antitumor abilities compared with nEPS. These findings provide a basis for using iEPSs as novel pharmaceutical agents for human therapies.

Nafamostat mesylate (NM), a synthetic serine protease inhibitor first placed on the market by Japan Tobacco in 1986, has been approved to treat inflammatory-related diseases, such as pancreatitis. Recently, an increasing number of studies have highlighted the promising effects of NM in inhibiting cancer progression. Alone or in combination treatments, studies have shown that NM attenuates various malignant tumors, including pancreatic, colorectal, gastric, gallbladder, and hepatocellular cancers. In this review, based on several activating pathways, including the canonical Nuclear factor-κB (NF-κB) signaling pathway, tumor necrosis factor receptor-1 (TNFR1) signaling pathway, and tumorigenesis-related tryptase secreted by mast cells, we summarize the anticancer properties of NM in existing studies both in vitro and in vivo. In addition, the efficacy and side effects of NM in cancer patients are summarized in detail. To further clarify NM's antitumor activities, clinical trials devoted to validating the clinical applications and underlying mechanisms are needed in the future.

Nafamostat mesylate (NM), a synthetic serine protease inhibitor first placed on the market by Japan Tobacco in 1986, has been approved to treat inflammatory-related diseases, such as pancreatitis. Recently, an increasing number of studies have highlighted the promising effects of NM in inhibiting cancer progression. Alone or in combination treatments, studies have shown that NM attenuates various malignant tumors, including pancreatic, colorectal, gastric, gallbladder, and hepatocellular cancers. In this review, based on several activating pathways, including the canonical Nuclear factor-κB (NF-κB) signaling pathway, tumor necrosis factor receptor-1 (TNFR1) signaling pathway, and tumorigenesis-related tryptase secreted by mast cells, we summarize the anticancer properties of NM in existing studies both in vitro and in vivo. In addition, the efficacy and side effects of NM in cancer patients are summarized in detail. To further clarify NM's antitumor activities, clinical trials devoted to validating the clinical applications and underlying mechanisms are needed in the future. [ABSTRACT FROM AUTHOR]

Deuterium substitution has been widely known that can improve the pharmacokinetic profiles due to isotope effect. Herein, a series of deuterated sorafenib derivatives have been synthesized and characterized by 1H NMR, 13C NMR and MS. Their antitumor activities were evaluated in vitro against human hepatoma cell line HepG2 and human cervical carcinoma cell line HeLa. The LogP values were detected by high-performance liquid chromatography. Subsequently, the metabolic stability and pharmacokinetics study were assessed in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Abstract Sixty-one novel steroidal imidazolium salt derivatives were synthesized and evaluated in vitro against a panel of human tumor cell lines. The results showed that diosgenin‒imidazolium salt derivatives displayed much higher cytotoxic activities than cholesterol‒imidazolium salts and dehydroepiandrosterone‒imidazolium salts. The SARs results suggested that the existence of substituted 5,6-dimethyl-benzimidazoles or benzimidazole ring and substitution of the imidazolyl-3α-position with a 2-bromobenzyl or 2-naphthylmethyl group could be critical for promoting cytotoxic activity. Diosgenin‒imidazolium salt a30 was found to be the most potent compound with IC 50 values of 0.44–0.79 μM against five human tumor cell lines. Compound a24 showed inhibitory activity selectively against SMMC-7721 cell lines with IC 50 value of 0.21 μM and 54-fold more sensitive to DDP. Moreover, compound a30 inhibited cell proliferation through inducing the G0/G1 cell cycle arrest and apoptosis in SMMC-7721 cells. Graphical abstract Image 1 Highlights • A series of sixty-one novel steroidal imidazolium salt derivatives were prepared. • Compound a30 was found to be the most potent compound with antitumor activity. • Compound a24 showed inhibitory activity selectively against SMMC-7721 cells. • The structure-activity relationship results of imidazolium salts were summarized. • Compound a30 induced the G0/G1 phase cell cycle arrest and apoptosis in SMMC-7721. [ABSTRACT FROM AUTHOR]

Abstract The complexes of oxovanadium(IV) with bidentate heterocyclic azo pyrazolone were synthesized and characterized by elemental analyses, IR, UV–Visible, EPR and magnetic measurements as well as thermal analysis and X-ray diffraction. Reaction of [VIVO(acac) 2 ] (where acac = acetylacetonate) in methanol with azo pyrazolones (HL n) produced mononuclear vanadium(IV) oxo complexes with general formula [VO(L n) 2 ]H 2 O. The molar conductance measurements proved that all the complexes are non-electrolytes. IR spectra showed that the ligands (HL n) acts as a monobasic bidentate ligand by coordinating via the nitrogen atom of the pyrazole ring (HN N =) and deprotonated hydroxyl O, thereby forming a square pyramidal chelating ring. Analytical data revealed that all the complexes exhibited 1:2 (metal-ligand) ratio. The thermal data confirm that the complexes have water molecule outside the coordination sphere and the complexes show similar thermogravimetric decomposition fragments which are consistent with the proposed structures. The thermodynamic parameters of VO(II) complexes are calculated using Coats–Redfern and Horowitz-Metzger methods. The optimized bond lengths, bond angles and the calculated quantum chemical parameters for VO(II) complexes (1 – 3) were investigated. Their interactions with calf thymus DNA were investigated by absorption spectra and viscosity measurements. The results suggest that these complexes bind to DNA in an intercalative mode (K b = 4.58–8.96 × 105 M−1). All VO(II) complexes (1 – 3) were evaluated against human cancer cell lines, MCF-7 and HepG-2 as compared with the positive controls in the viability assay of colchicine and vinblastine. Complex 2 (IC 50 = 30.5 ± 2.3 and 20.1 ± 1.9 μg/ml) exhibit moderate activities against the two cell lines MCF-7 and HepG-2, respectively as compared to the Colchicine (IC 50 = 17.7 ± 0.03 and 10.6 ± 0.01 μg/mL). The antimicrobial activities of VO(II) complexes were tested against gram negative bacteria (Escherichia coli) , gram positive bacteria (Staphylococcus aureus) and fungal (Candida albicans). Graphical abstract Image 10140 Highlights • Oxovanadium(IV) complexes. • Calf-thymus DNA binding studies. • Thermodynamic parameters. • Cytotoxicity, antioxidant and antimicobial activities. [ABSTRACT FROM AUTHOR]

This study reports a novel and efficient method for the synthesis of the first reported novel class of pyrazole thioglycosides 6a–h. These series of compounds were designed through the reaction of sodium 2-cyano-3-oxo-3-(4-substitutedphenylamino)prop-1-ene-1,1-bis(thiolate) salts 2 with hydrazine hydrate in ethanol at room temperature to give the corresponding sodium 5-amino-4-(substitutedphenylcarbamoyl)-1H-pyrazole-3-thiolates 3a–d. The latter compounds were treated with protected α-D-gluco- and galacto-pyranosyl bromides 4a,b in DMF at ambient temperature to give in a high yields the corresponding pyrazole thioglycosides 6a–h. Treatment of pyrazole salts 3a–d with hydrochloric acid at amobient temperature afforded the corresponding 3-mercaptopyrazole derivatives 5. The latter compounds were treated with peracetylated sugars 4 in sodium hydride in ethanol at ambient temperature to tolerate the S-glycosyl 6a–h compounds. Ammonolysis of the pyrazole thioglycosides 6a–h afforded the corresponding free thioglycosides 7a–h. The toxicity and antitumor activities of the synthesized compounds were studied. [ABSTRACT FROM AUTHOR]

Graphical abstract The selectivity of synthesized polynuclear copper(II) complexes with nalidixic acid hydrazone derivatives, as shown for complex 1A , [Cu 2 (C 16 H 16 N 6 O 2)Cl 4 ], and their "spaceship-like" structures inspired this graphical abstract where complex 1A locks on a cancer cell. Highlights • Copper(II) complexes with nalidixic acid hydrazone derivatives were synthesized. • Antitumoral activities were evaluated in vitro against a panel of tumor cell lines. • Compared to controls (C+), complexes were more active and selective in general. • Biological profiles suggest different targets for the complexes when compared to C+. • Cu 2 (C 16 H 16 N 6 O 2)Cl 4 complex (1A) is a cell cycle non-specific drug for NCI-ADR/RES. Abstract Polynuclear copper(II) complexes with nalidixic acid hydrazones derivatives containing 2-imidazolyl (h2imi, complexes 1A and 1B), 4-imidazolyl (h4imi, complexes 2A and 2B), salicyl (hsali, complex 3) and 1H-pyrrolyl (hpyrr, complex 4) units were synthesized and characterized by chemical and spectroscopic methods. Crystallographic studies of complex 1B , [Cu 3 (h2imi−) 2 Cl 4 ], show that coordination of hydrazones to Cu(II) occurs by tridentate modes of the type κ3(O,N,N′) as well as bidentate modes of the type κ2(O′,N″). For complexes 2A and 4 , EPR data are compatible with a trinuclear structure, based on an antiferromagnetic coupling between copper centers that is stronger at low temperature. Complexes 1A , 2A , 3 and 4 had their antiproliferative activities evaluated in vitro against a panel of tumor cells by determination of GI 50 values. Complexes 3 (GI 50 = 1.14 μM, SI = 4.52) and 4 (GI 50 = 2.72 μM, SI = 6.06) were more active and selective against 786-0 cell lines than doxorubicin (GI 50 = 85.0 μM, SI = 5·10−3). Complex 1A presented high selectivity indexes against glioma (U251, GI 50 = 2.53 μM, SI = 60.9) and multiple drugs resistance ovarian (NCI/ADR-RES GI 50 = 1.69 μM, SI = 91.4) cell lines when compared to doxorubicin and cisplatin. DNA gel electrophoresis (pIRES DNA) and cell-cycle arrest (NCI/ADR-RES cell line) assays were performed with complex 1A. The obtained results suggest that the mechanism of action of complex 1A does not involve DNA interaction and complex 1A seems to be a cell cycle non-specific drug. [ABSTRACT FROM AUTHOR]

Abstract A novel approach was employed for the synthesis of un-doped tinoxide and Cobalt-doped tinoxide (Co-doped SnO 2) nanoparticles (NAPs) by using aqueous extract of Clerodendrum inerme with the help of eco-friendly superficial solution combustion method. Synthesized NAPs were characterized by different spectroscopic techniques and results from XRD, TEM, SEM, EDX and UV–Vis examines confirmed the successful synthesis, crystalline nature and spherical structure of un-doped SnO 2 and Co-doped SnO 2 NAPs with the average grain size of 30 and 40 nm; and band gap energy of 3.68 and 2.76 eV respectively. Antimicrobial propensity of the synthesized NAPs was determined by agar well assay, SEM, TEM and confocal laser scanning microscopic analysis against various bacterial and fungal strains. Synthesized Co-doped SnO 2 NAPs were unveiled the extraordinary antibacterial and antifungal activities against E. coli , B. subtilis , A. niger, A. flavus, and C. albicans with the zone of inhibitions of 30 ± 0.08 mm and 26 ± 0.06 mm, 17 ± 0.04 mm, 23 ± 0.08 mm and 26 ± 0.06 respectively which were also evidenced from SEM, TEM and confocal laser scanning microscopy. In addition, green synthesized Co-doped SnO 2 NAPs were demonstrated the substantial antioxidant activity by scavenging DPPH, significant in vitro anticancer and in vivo antitumor activity on breast carcinoma cells (MCF-7) and Ehrlich ascites tumor cell lines respectively than standard. The hemolytic activity disclosed low cytotoxicity of fabricated NAPs (0.89 ± 0.05%) at 5 mg/mL, which was indicated their biocompatibility potential. Hence, the multi-purpose properties of synthesized NAPs presented in the current study can be further deliberated for pharmaceutical and nanomedicine applications. Graphical abstract Image 1 Highlights • Un-doped SnO 2 and Co-doped SnO 2 were synthesized by green approach. • They were synthesized using solution combustion method in which leaves extract of C. inerme act as a fuel. • Synthesized Co-doped SnO 2 possess potent and enhanced antibacterial, antifungal, and anticancer properties. • Biological activities are directly linked to the physical characteristics of synthesized nanoparticles. • The results indicate that Co-doped SnO 2 will prove good candidates for future therapeutic applications. [ABSTRACT FROM AUTHOR]

Complexes of [Cu(SCN) 2 (3-Acpy) 2 ], (1) and [Co(SCN) 2 (H 2 O) 2 (3-Acpy) 2 ], (2) were synthesized and structurally characterized by single crystal X-ray diffraction and spectroscopic methods. Through hydrogen bonding, the discrete units of complexes 1 and 2 extend to form a 3D supramolecular network. Complexes 1 and 2 were evaluated to determine whether they were able to inhibit the growth of liver cancer (HepG2 cells) and breast cancer (MCF-7 cells). Complex 1 exhibits lower IC 50 values than complex 2 against both of two human cell lines. [Display omitted] Complexes of [Cu(SCN) 2 (3-Acpy) 2 ], (1) and [Co(SCN) 2 (H 2 O) 2 (3-Acpy) 2 ], (2) were synthesized at ambient temperature by adding an aqueous solution of copper(II) or cobalt(II) chloride to H 2 O/CH 3 CN solution of 3-acetlpyridine (3-Acpy) and potassium thiocyanate. Elemental analysis, FT-IR and UV–vis spectra were used to comprehensively characterize complexes 1 and 2. Single crystal X-ray diffraction was used to analyze the crystal structure of complexes 1 and 2. In complex 1 , the copper is bonded to two 3-Acpy ligands and two thiocyanates groups in trans mode giving square planer geometry. While, in complex 2 , the cobalt ion is coordinated to two water molecules, two 3-Acpy ligands and two thiocyanates ions in trans mode giving an octahedral structure. Through hydrogen bonding, the discrete units of complexes 1 and 2 extend to form a 3D supramolecular network. Additionally, the luminescence spectra of complexes 1 and 2 were investigated. Complexes 1 and 2 were evaluated to determine whether they were able to inhibit the growth of liver cancer (HepG2 cells) and breast cancer (MCF-7 cells). Complex 1 exhibits lower IC 50 values than complex 2 against both of the two human cell lines. In HepG2 cells treated with complexes 1 and 2 at dosages roughly half of the IC 50 , apoptosis of complexes 1 and 2 is triggered by 18% and 22%, respectively. It was found that copper complex 1 has a greater cytotoxic effect on MCF-7 and influences on late apoptosis of HepG2. [ABSTRACT FROM AUTHOR]

Marsdenia tenacissima (MT), a traditional Chinese herbal medicine, has long been used for thousands of years to treat asthma, tracheitis, rheumatism, etc. An increasing number of recent studies have focused on the antitumor effects of MT. The effects of MT on cancer are the result of various activated signaling pathways and inhibiting factors and the high expression levels of regulatory proteins. MT can inhibit different cancer types including non-small cell lung cancer (NSCLC), malignant tumors, hepatic carcinoma, and so on. This article mainly focuses on the activities and mechanisms of MT. In addition, the efficacy and toxicity of MT are also discussed. Further studies of MT are required for improved medicinal utilization.

Marine organisms are rich sources of bioactive compounds and their biotechnological potential attracted the attention to biologists and chemists all over the world. During the first decade of the 21st century alone, over 2000 molecules from cnidarians were described. The phylum cnidaria (corals, sea pens, sea anemones, jellyfish and hydroids) includes over 10,000 species living in aquatic habitats. Cnidarians are the oldest venomous animals. In this phylum, most toxicological studies have been done in Anthozoa. The Soft corals Alcyonacea and Gorgonacea orders of Anthozoa represent by far the highest number of species yielding promising compounds. Up to now, numerous chemical components have been isolated from cnidarians, including steroids, diterpenoids and sesquiterpenoids have been shown to exhibit biological properties such as antimicrobial, antitumor activities and cytotoxicity. In this review, we summarize some studies that focus on some of the most promising marine bioactive isolated from cindirians in last decade.

The biosynthesis method is thought to be clean, nontoxic and environmentally acceptable. Many microorganisms produce extracellular or intracellular metal nanoparticles with different efficiency, size and shape. The goal in this study is to control the size of silver nanoparticles. The preliminary screening of microorganisms, Fusarium oxysporum was selected to control size of silver nanoparticles. Parametric optimization showed smallest particle size when F. oxysporum treated with 10−2 M silver nitrate (metal ion concentration) at 50°C with 11 g wet biomass at pH 6 when fungal age 7 days when incubated for 72 h silver nanoparticles produced was characterized by TEM which revealed the formation of spherical, well-dispersed nanoparticles with size between 5 and 13 nm and FTIR gives the bands at 1619 and 1392.5 corresponding to the binding vibration of amide I and II bands of proteins, respectively. Antibacterial activity against Escherichia coli and Staphylococcus aureus showed maximum zone of inhibition of 2 mm and 1.6 mm, respectively, at 80 µL of silver nanoparticles. Cytotoxic activity was expressed as IC50 that is found to be 121.23 µg cm−3.