IN-VITRO THROMBOLYTIC ACTIVITY OF HERBAL ANTI-ARTHEROSCLEROSIS FORMULATION

In recent study, the Herbal Anti-atherosclerosis Formulation comprising of Lemon, Garlic, Ginger and Apple fruit extract vinegar have been generally recognized as agents for prevention and treatment of cardiovascular and other metabolic ailments, atherosclerosis, hyperlipidemia, thrombosis, hypertension and diabetes and cholesterol bringing down impact. Accordingly, the present study was intended to investigate thrombolytic properties of Herbal Anti-atherosclerosis Formulation. Natural Antiatherosclerosis Formulation of demonstrated exceptionally huge (P <0.001) clot lytic properties in different blood samples. The percent clot lytic activity was compared with negative control (water) and standard enzyme positive control (streptokinase). The mean % of clot lysis for water and streptokinase was discovered 4.71% and 86.21% individually. Then again the mean percent clot lytic activity of Herbal Anti-atherosclerosis Formulation was discovered 29.51%, which is huge contrast and the positive and negative control. The present research recommends that Herbal Anti-atherosclerosis Formulation has significant thrombolytic action. Consequently the detailing may be a wellspring of powerful natural medication

IN-VITRO THROMBOLYTIC ACTIVITY OF HERBAL ANTI-ARTHEROSCLEROSIS FORMULATION

In recent study, the Herbal Anti-atherosclerosis Formulation comprising of Lemon, Garlic, Ginger and Apple fruit extract vinegar have been generally recognized as agents for prevention and treatment of cardiovascular and other metabolic ailments, atherosclerosis, hyperlipidemia, thrombosis, hypertension and diabetes and cholesterol bringing down impact. Accordingly, the present study was intended to investigate thrombolytic properties of Herbal Anti-atherosclerosis Formulation. Natural Antiatherosclerosis Formulation of demonstrated exceptionally huge (P <0.001) clot lytic properties in different blood samples. The percent clot lytic activity was compared with negative control (water) and standard enzyme positive control (streptokinase). The mean % of clot lysis for water and streptokinase was discovered 4.71% and 86.21% individually. Then again the mean percent clot lytic activity of Herbal Anti-atherosclerosis Formulation was discovered 29.51%, which is huge contrast and the positive and negative control. The present research recommends that Herbal Anti-atherosclerosis Formulation has significant thrombolytic action. Consequently the detailing may be a wellspring of powerful natural medication

Design, and synthesis of selectively anticancer 4-cyanophenyl substituted thiazol-2-ylhydrazones

Cyclization of substituted thiosemicarbazones with α-bromo-4-cyanoacetophenone allows rapid single-step sustainable syntheses of 4-cyanophenyl-2-hydrazinylthiazoles libraries (30 examples, 66–79%). All show anticancer efficacy against HCT-116 and MCF-7 carcinoma cell lines with the majority being more active than cisplatin positive controls. The compounds 2-(2-(2-hydroxy-3-methylbenzylidene) hydrazinyl)-4-(4-cyanophenyl)thiazole (3f) and 2-(2-((pentafluorophenyl)methylene)-hydrazinyl)-4-(4-cyanophenyl) thiazole (3a′) show optimal GI50 values (1.0 ± 0.1 μM and 1.7 ± 0.3 μM) against MCF-7 breast cancer cells. Against colorectal carcinoma HCT-116 cells, (2-(2-(3-bromothiophen-2yl)methylene)hydrazinyl)-4-(4-cyanophenyl)thiazole (3b′), 2-(2-(2-hydroxy-3-methylbenzylidene) hydrazinyl)-4-(4-cyanophenyl)thiazole (3f), 2-(2-(2,6-dichlorobenzylidene)hydrazinyl)-4-(4-cyanophenyl)thiazole (3f) and 2-(2-(1-(4-fluorophenyl)ethylidene)hydrazinyl)-4-(4-cyanophenyl) thiazole (3w) are the most active (GI50 values: 1.6 ± 0.2, 1.6 ± 0.1, 1.1 ± 0.5 and 1.5 ± 0.8 μM respectively). Control studies with MRC-5 cells indicate appreciable selectivity towards the cancer cells targeted. Significant (p < 0.005) growth inhibition and cytotoxicity effects for the thiazoles 3 were corroborated by cell count and clonogenic assays using the same cancer cell lines at 5 and 10 μM agent concentrations. Cell cycle, caspase activation and Western blot assays demonstrated that compounds 3b′ and 3f induce cancer cell death via caspase-dependent apoptosis. The combination of straight forward synthesis and high activity makes the thiazoles 3 an interesting lead for further development

In Vitro Anticancer Properties of Novel Bis-Triazoles

Here, we describe the anticancer activity of our novel bis-triazoles MS47 and MS49, developed previously as G-quadruplex stabilizers, focusing specifically upon the human melanoma MDA-MB-435 cell line. At the National Cancer Institute (NCI), USA, bis-triazole MS47 (NCS 778438) was evaluated against a panel of sixty human cancer cell lines, and showed selective, distinct multi-log differential patterns of activity, with GI50 and LC50 values in the sub-micromolar range against human cancer cells. MS47 showed highly selective cytotoxicity towards human melanoma, ovarian, CNS and colon cancer cell lines; in contrast, the leukemia cell lines interestingly showed resistance to MS47 cytotoxic activity. Further studies revealed the potent cell growth inhibiting properties of MS47 and MS49 against the human melanoma MDA-MB-435 cell line, as verified by MTT assays; both ligands were more potent against cancer cells than MRC-5 fetal lung fibroblasts (SI > 9). Melanoma colony formation was significantly suppressed by MS47 and MS49, and time- and dose-dependent apoptosis induction was also observed. Furthermore, MS47 significantly arrested melanoma cells at the G0/G1 cell cycle phase. While the expression levels of Hsp90 protein in melanoma cells were significantly decreased by MS49, corroborating its binding to the G4-DNA promoter of the Hsp90 gene. Both ligands failed to induce senescence in the human melanoma cells after 72 h of treatment, corroborating their weak stabilization of the telomeric G4-DNA

Cardiac glycoside cerberin exerts anticancer activity through PI3K/AKT/mTOR signal transduction inhibition

Natural products possess a significant role in anticancer therapy and many currently-used anticancer drugs are of natural origin. Cerberin (CR), a cardenolide isolated from the fruit kernel of Cerbera odollam, was found to potently inhibit cancer cell growth (GI 50 values 60% bioavailability and rapid absorption; doses of 1–10 mg/kg CR were predicted to maintain efficacious unbound plasma concentrations (>GI 50 value). CR's potent and selective anti-tumour activity, and its targeting of key signalling mechanisms pertinent to tumourigenesis support further preclinical evaluation of this cardiac glycoside

Discovery of a highly active anticancer analogue of cardamonin that acts as an inducer of caspase-dependent apoptosis and modulator of the mTOR pathway

Nineteen analogues of cardamonin were semi-synthesized and tested against A549 and HK1 cell lines. The analogues were fully characterized via IR and NMR analyses, while compound 19 (a Cu (II) complex of cardamonin) was further characterized via HRMS, ELEMENTAL ANALYSIS, TGA and UV-VIS spectroscopy. Results of the MTS cell viability assay showed that several derivatives possessed cytotoxic activities that were several-fold more potent than cardamonin. Compound 19 was the most potent analogue possessing IC50 values of 13.2 µM and 0.7 µM against A549 and HK1 cells, corresponding to a 5- and 32-fold increase in activity, respectively. Furthermore, the active analogues, especially 19, have generally demonstrated lower toxicity towards normal MRC5 cells. SAR analysis showed the importance of the ketone and alkene groups for bioactivity, while substituting cardamonin’s phenolic groups with more polar moieties resulted in activity enhancement. As part of the SAR study and further exploration of chemical space, the effect of metal coordination on cytotoxicity was also investigated, but it was only possible to successfully obtain the Cu (II) complex of cardamonin (19), and results showed that the metal ion enhanced activity. 19 was also able to significantly inhibit the migration of A549 and HK1 cells. Further studies have shown that the most active analogue, 19, induced DNA damage resulting in G2/M-phase cell-cycle arrest in both cell lines. These events further led to the induction of apoptosis by 19 via caspase-3/7 and caspase-9 activation, PARP cleavage and downregulation of Mcl-1 expression. Finally, 19 inhibited the expression levels of p-mTOR and p-4EBP1. These data indicated that 19 exerted its anticancer activity, at least in part, via inhibition of the mTOR signalling pathway

Antiviral activity of Embelia ribes Burm. f. against influenza virus invitro

AbstractViral respiratory infections are raising serious concern globally. Asian medicinal plants could be useful in improving thecurrent treatment strategies for influenza. The present study examines the activity of five plants from Bangladesh againstinfluenza virus. MDCK cells infected with influenza virus A/Puerto Rico/8/34 (H1N1) were treated with increasing concentrationsof ethyl acetate extracts, and their cytotoxicity (CC50), virus-inhibiting activity (IC50), and selectivity index (SI) werecalculated. The ethyl acetate extract of fruits of Embelia ribes Burm. f. (Myrsinaceae) had the highest antiviral activity, withan IC50of 0.2 ?g/mL and a SI of 32. Its major constituent, embelin, was further isolated and tested against the same virus.Embelin demonstrated antiviral activity, with an IC50of 0.3 ?M and an SI of 10. Time-of-addition experiments revealed thatembelin was most effective when added at early stages of the viral life cycle (0-1 h postinfection). Embelin was further evaluatedagainst a panel of influenza viruses including influenza A and B viruses that were susceptible or resistant to rimantadineand oseltamivir. Among the viruses tested, avian influenza virus A/mallard/Pennsylvania/10218/84 (H5N2) was the mostsusceptible to embelin (SI = 31), while A/Aichi/2/68 (H3N2) virus was the most resistant (SI = 5). In silico molecular dockingshowed that the binding site for embelin is located in the receptor-binding domain of the viral hemagglutinin. The results ofthis study provide evidence that E. ribes can be used for development of a novel alternative anti-influenza plant-based agent

Novel Semi-Synthetic Cu (II)–Cardamonin Complex Exerts Potent Anticancer Activity against Triple-Negative Breast and Pancreatic Cancer Cells via Inhibition of the Akt Signaling Pathway

Cardamonin is a polyphenolic natural product that has been shown to possess cytotoxic activity against a variety of cancer cell lines. We previously reported the semi-synthesis of a novel Cu (II)–cardamonin complex (19) that demonstrated potent antitumour activity. In this study, we further investigated the bioactivity of 19 against MDA-MB-468 and PANC-1 cancer cells in an attempt to discover an effective treatment for triple-negative breast cancer (TNBC) and pancreatic cancer, respectively. Results revealed that 19 abolished the formation of MDA-MB-468 and PANC-1 colonies, exerted growth-inhibitory activity, and inhibited cancer cell migration. Further mechanistic studies showed that 19 induced DNA damage resulting in gap 2 (G2)/mitosis (M) phase arrest and microtubule network disruption. Moreover, 19 generated reactive oxygen species (ROS) that may contribute to induction of apoptosis, corroborated by activation of caspase-3/7, PARP cleavage, and downregulation of Mcl-1. Complex 19 also decreased the expression levels of p-Akt and p-4EBP1, which indicates that the compound exerts its activity, at least in part, via inhibition of Akt signalling. Furthermore, 19 decreased the expression of c-Myc in PANC-1 cells only, which suggests that it may exert its bioactivity via multiple mechanisms of action. These results demonstrate the potential of 19 as a therapeutic agent for TNBC and pancreatic cancer