Evaluation Of Antiproliferative Activity Research Articles

Cobalt and iron bis(dicarbollide) conjugates with cholesterol: synthesis and evaluation of antiproliferative activity

Cobalt and iron bis(dicarbollide) conjugates with cholesterol: synthesis and evaluation of antiproliferative activity

Enzymatic Synthesis of 2-Chloropurine Arabinonucleosides with Chiral Amino Acid Amides at the C6 Position and an Evaluation of Antiproliferative Activity In Vitro

A number of purine arabinosides containing chiral amino acid amides at the C6 position of the purine were synthesized using a transglycosylation reaction with recombinant E. coli nucleoside phosphorylases. Arsenolysis of 2-chloropurine ribosides with chiral amino acid amides at C6 was used for the enzymatic synthesis, and the reaction equilibrium shifted towards the synthesis of arabinonucleosides. The synthesized nucleosides were shown to be resistant to the action of E. coli adenosine deaminase. The antiproliferative activity of the synthesized nucleosides was studied on human acute myeloid leukemia cell line U937. Among all the compounds, the serine derivative exhibited an activity level (IC50 = 16 μM) close to that of Nelarabine (IC50 = 3 μM) and was evaluated as active.

Development of novel anilinoquinazoline-based carboxylic acids as non-classical carbonic anhydrase IX and XII inhibitors

As part of our ongoing endeavour to identify novel inhibitors of cancer-associated CA isoforms IX and XII as possible anticancer candidates, here we describe the design and synthesis of small library of 2-aryl-quinazolin-4-yl aminobenzoic acid derivatives (6a–c, 7a–c, and 8a–c) as new non-classical CA inhibitors. On account of its significance in the anticancer drug discovery and in the development of effective CAIs, the 4-anilinoquinazoline privileged scaffold was exploited in this study. Thereafter, the free carboxylic acid functionality was appended in the ortho (6a–c), meta (7a–c), or para-positon (8a–c) of the anilino motif to furnish the target inhibitors. All compounds were assessed for their inhibitory activities against the hCA I, II (cytosolic), IX, and XII (trans-membrane, tumour-associated) isoforms. Moreover, six quinazolines (6a–c, 7b, and 8a–b) were chosen by the NCI-USA for in vitro anti-proliferative activity evaluation against 59 human cancer cell lines representing nine tumour subpanels.

Formulation and evaluation of herbal sunscreen

Due to the hasty-paced life of today, our life is affected by pollution and harsh synthetic chemicals, hence, nature has rendered us with its everlasting notable ingredients of herbal. The major cause of sunburn is UV rays which leads to precarious skin cancer. Sunscreen is a topical product that absorbs or reflects some of the sun’s UV radiation on the skin from excessive exposure to UV radiation. It has the potential to prevent sunburn & reduce the harmful effects of the sun such as premature aging & skin cancer. The Present research work portrays the formulations & evaluation of topical photoprotective, containing antioxidant, anti-malignant, wound healing, antifungal, antiaging, moisturizer, anti-inflammatory, antiproliferative activity, and other photo-protective polyphenols. The present research work renders a stable natural photoprotective formulation with antioxidant properties, high SPF, and more indispensable homogenous UVA/UVB protection.

Identification of Lilium ledebourii antiproliferative compounds against skin, bone and oral cancer cells.

This study aimed at the evaluation of anti antiproliferative activity of Lonicera nummularifolia, Lilium ledebourii, Campsis radicans and Parthenocissus quinquefolia extracts. The extract was taken from the fresh leaves and bulbs of the plants by maceration method in the dark. After separating the solvent, the remaining dry matter was added to the culture medium containing G292, A431 and KB cancer and HGF-1 normal cells. Cytotoxicity tests, as well as cell cycle and apoptosis tests were performed on cells treated with dry substances and untreated cells. Finally, the most effective extract was separated into fractions by preparative HPLC and the effective fraction was characterized by Triple-Quad LC/MS connected to the UHPLC system. All extracts significantly enhanced cell death rate in the three cancer cell lines more than the HGF-1 line. The Methanolic extract of L. ledebourii bulbs exhibited considerable efficacy on apoptosis induction in the cancer cell lines. It seems that the mode of action for L. ledebourii methanolic extract is mediated through increased BID/MAPK14 expression and decreased MDM2/BCL2/MYC expression, which led to activation of the p53 protein-induced apoptosis. It was also determined that the effective fraction of L. ledebourii methanolic extract consists of substances such as caffeic acid, ferulic acid, coumarin acid, catechin and apigenin. Overall, the findings suggest that L. ledebourii is a promising source of bioactive compounds with anticancer properties.

Screening Evaluation of Antiproliferative, Antimicrobial and Antioxidant Activity of Lichen Extracts and Secondary Metabolites In Vitro.

Lichen metabolites represent a wide range of substances with a variety of biological effects. The present study was designed to analyze the potential antiproliferative, antimicrobial and antioxidative effects of several extracts from lichens (Pseudevernia furfuracea, Lobaria pulmonaria, Cetraria islandica, Evernia prunastri, Stereocaulon tomentosum, Xanthoria elegans and Umbilicaria hirsuta) and their secondary metabolites (atranorin, physodic acid, evernic acid and gyrophoric acid). The crude extract, as well as the isolated metabolites, showed potent antiproliferative, cytotoxic activity on a broad range of cancer cell lines in 2D (monolayer) and 3D (spheroid) models. Furthermore, antioxidant (2,2-diphenyl-1-picryl-hydrazylhydrate (DPPH) and in vitro antimicrobial activities were assessed. Data showed that the lichen extracts, as well as the compounds present, possessed biological potential in the studied assays. It was also observed that the extracts were more efficient and their major compounds showed strong effects as antiproliferative, antioxidant and antibacterial agents. Moreover, we demonstrated the 2D and 3D models' importance to drug discovery for further in vivo studies. Despite the fact that lichen compounds have been neglected by the scientific community for long periods, nowadays they are objects of investigation based on their promising effects.

Synthesis and evaluation of antiproliferative activities of indole aza carbolines

Synthesis and evaluation of antiproliferative activities of indole aza carbolines

Discovery of Novel 3,11-Bispeptide Ester Arenobufagin Derivatives with Potential in Vivo Antitumor Activity and Reduced Cardiotoxicity.

Arenobufagin, one of the bufadienolides isolated from traditional Chinese medicine Chan'su, exhibits potent antitumor activity. However, serious toxicity and small therapeutic window limits its drug development. In the present study, to our knowledge, novel 3,11-bispeptide ester arenobufagin derivatives have been firstly designed and synthesized on the base of our previous discovery of active 3-monopeptide ester derivative. The in vitro antiproliferative activity evaluation revealed that the moiety at C3 and C11 hydroxy had an important influence on cytotoxic activity and selectivity. Compound ZM350 notably inhibited tumor growth by 58.8 % at a dose 10 mg/kg in an A549 nude mice xenograft model. Therefore, compound ZM350 also presented a concentration-dependent apoptosis induction and low inhibitory effect against both hERG potassium channel and Cav1.2 calcium channel. Our study suggests that novel 3,11-bispeptide ester derivatives will be a potential benefit to further antitumor agent development of arenobufagin.

Antiproliferative activity and toxicity evaluation of 1,2,3-triazole and 4-methyl coumarin hybrids in the MCF7 breast cancer cell line.

Four coumarin-triazole hybrids were selected from our in house library and screened for cytotoxic activity on A549 (lung cancer), HepG2 (liver cancer), J774A1 (mouse sarcoma macrophage), MCF7 (breast cancer), OVACAR (ovarian cancer), RAW (murine leukaemia macrophage), and SiHa (uterus carcinoma) and their in vitro toxicity was assessed on 3T3 (healthy fibroblasts) cell lines. SwissADME pharmacokinetic prediction was performed. Effects on ROS production, mitochondrial membrane potential, apoptosis/necrosis and DNA damage were evaluated. All of the hybrids have good pharmacokinetic predictions. Each of them showed cytotoxic activity against the MCF7 breast cancer cell line, with IC50 between 2.66 and 10.08 μM, lower than cisplatin (45.33 μM) for the same test. One can observe an order of reactivity from the most potent: LaSOM 186 > LaSOM 190 > LaSOM 185 > LaSOM 180, with a better selectivity index than the reference drug cisplatin and the precursor hymecromone, and caused cell death by apoptosis induction. Two compounds showed antioxidant activity in vitro and three disrupted the mitochondrial membrane potential. None of the hybrids caused genotoxic damage to healthy 3T3 cells. All hybrids showed potential for further optimization, mechanism elucidation, in vivo activity and toxicity tests.

Synthesis and evaluation of antiproliferative and mPGES-1 inhibitory activities of novel carvacrol-triazole conjugates

Synthesis and evaluation of antiproliferative and mPGES-1 inhibitory activities of novel carvacrol-triazole conjugates

Green Synthesis of Silver Nanoparticles Using Randia aculeata L. Cell Culture Extracts, Characterization, and Evaluation of Antibacterial and Antiproliferative Activity.

The demand for metallic nanoparticles synthesized using green methods has increased due to their various therapeutic and clinical applications, and plant biotechnology may be a potential resource facilitating sustainable methods of AgNPs synthesis. In this study, we evaluate the capacity of extracts from Randia aculeata cell suspension culture (CSC) in the synthesis of AgNPs at different pH values, and their activity against pathogenic bacteria and cancer cells was evaluated. Using aqueous CSC extracts, AgNPs were synthesized with 10% (w/v) of fresh biomass and AgNO3 (1 mM) at a ratio of 1:1 for 24 h of incubation and constant agitation. UV-vis analysis showed a high concentration of AgNPs as the pH increased, and TEM analysis showed polydisperse nanoparticles with sizes from 10 to 90 nm. Moreover, CSC extracts produce reducing agents such as phenolic compounds (162.2 ± 27.9 mg gallic acid equivalent/100 g biomass) and flavonoids (122.07 ± 8.2 mg quercetin equivalent/100 g biomass). Notably, AgNPs had strong activity against E. coli, S. pyogenes, P. aeruginosa, S. aureus, and S. typhimurium, mainly with AgNPs at pH 6 (MIC: 1.6 to 3.9 µg/mL). AgNPs at pH 6 and 10 had a high antiproliferative effect on cancer cells (IC50 < 5.7 µg/mL). Therefore, the use of cell suspension cultures may be a sustainable option for the green synthesis of AgNPs.

Thienopyrimidine-based agents bearing diphenylurea: Design, synthesis, and evaluation of antiproliferative and antiangiogenic activity.

An important role has been considered forthe vascular endothelial growth factor receptor 2 (VEGFR-2) in the angiogenesis process, so that its inhibition is an important scientific way for cancer treatment. In this work, new thienopyrimidine derivatives were synthesized and evaluated. Compared with sorafenib, the majority of the target compounds had antiproliferative activity against the PC3, HepG2, MCF7, SW480, and HUVEC cell lines, especially 9h with IC50 values of 4.5-15.1 μM, confirming the noticeable cytotoxic effects on the listed cell lines (PC3, HepG2, SW480, and HUVEC). Analyses by flow cytometry on SW480 and HUVEC cells revealed that 9n, 9k, 9h, and 9q led to apoptotic cell death. The result of the chick chorioallantoic membrane assay showed that 9h effectively reduced the number of corresponding blood vessels. Finally, the inhibitory effect on VEGFR-2 phosphorylation was considered as the outcome of Western blot analysis of compound 9h.

Design, synthesis and evaluation of novel dehydroabietic acid-dithiocarbamate hybrids as potential multi-targeted compounds for tumor cytotoxicity

In the present study, novel representatives of the important group of biologically-active, dehydroabietic acid-bearing dithiocarbamate moiety, were synthesized and characterized by 1 H NMR, 13 C NMR, HR-MS. The in vitro antiproliferative activity evaluation (MTT) indicated that these compounds exhibited potent inhibitory activities in various cancer cell lines (HepG-2, MCF-7, HeLa, T-24, MGC-803). Particularly, compound III -b possessed extraordinary cytotoxicity with low micromolar IC 50 values ranging from 4.07 to 38.84 µM against tested cancer cell lines, while displayed weak cytotoxicity on two normal cell lines (LO-2 and HEK 293 T). Subsequently, the potential mechanisms of representative compound III -b were elementarily investigated by Transwell experiment, which showed III -b can inhibit cancer cells migration. Annexin-V/PI dual staining showed that the compound can induce HepG-2 cells apoptosis in a dose-dependent manner. Meanwhile this apoptosis may be related to the upregulated protein expression of cleaved-caspase 3, cleaved-caspase 9, Bax and downregulated of Bcl-2 indicated by Western Blot. Later study further confirmed that ROS levels in HepG-2 cells increased significantly with the rise of concentrations. In addition, through the network pharmacology data analyzing, the core targets and signaling pathways of compound III -b for treatment of liver neoplasms were forecasted. Molecular docking model showed that compound III -b had high affinity with hub targets (CASP3, EGFR, HSP90AA1, MAPK1, ERBB2, MDM2), suggesting that compound III -b might target the hub protein to modulate signaling activity. Taken together, these data indicated that dehydroabietic acid structural modification following the “Molecular hybridization” principle is a feasible way to discover the potential multi-targeted antitumor compounds.

Evaluation of Anti-cancer and Anti-proliferative Activity of Medicinal Plant Extracts (Saffron, Green Tea, Clove, Fenugreek) on Toll Like Receptors Pathway

Evaluation of Anti-cancer and Anti-proliferative Activity of Medicinal Plant Extracts (Saffron, Green Tea, Clove, Fenugreek) on Toll Like Receptors Pathway

Acetogenins from the stems of Uvaria micrantha showing antiproliferative effects on HepG2 liver cancer cells

Five mono-tetrahydrofuran acetogenins: uvamicranins A–E and three known mono-tetrahydrofuran acetogenins; reticulatacin, calamistrin A, and uvarigrin, were isolated from the stems of Uvaria micrantha (Annonaceae). Their structures were elucidated by 2D NMR and high-resolution mass spectral analysis. The absolute configurations of uvamicranins A and B were determined by modified Mosher's method. Evaluation of antiproliferative activity of the isolated compounds showed that they were more potent towards the human hepatocellular carcinoma cell line HepG2, compared to the five other tested cell lines. Among the tested compounds, uvamicranin B (UvB) and uvarigrin (Uv) possessed strong antiproliferative activity with IC50 values of 2.89 ± 0.71 μM and 0.37 ± 0.06 μM, respectively. The antiproliferative mechanism of UvB and Uv, was investigated in HepG2 cell line showing that both compounds marginally induced apoptotic cell death, but exhibited cytostatic effect through induction of cell cycle arrest at the G2/M phase.

Synthesis and Evaluation of Antiproliferative Activity, Topoisomerase IIα Inhibition, DNA Binding and Non-Clinical Toxicity of New Acridine-Thiosemicarbazone Derivatives.

In this study, we report the synthesis of twenty new acridine–thiosemicarbazone derivatives and their antiproliferative activities. Mechanisms of action such as the inhibition of topoisomerase IIα and the interaction with DNA have been studied for some of the most active derivatives by means of both in silico and in vitro methods, and evaluations of the non-clinical toxicities (in vivo) in mice. In general, the compounds showed greater cytotoxicity against B16-F10 cells, with the highest potency for DL-08 (IC50 = 14.79 µM). Derivatives DL-01 (77%), DL-07 (74%) and DL-08 (79%) showed interesting inhibition of topoisomerase IIα when compared to amsacrine, at 100 µM. In silico studies proposed the way of bonding of these compounds and a possible stereoelectronic reason for the absence of enzymatic activity for CL-07 and DL-06. Interactions with DNA presented different spectroscopic effects and indicate that the compound CL-07 has higher affinity for DNA (Kb = 4.75 × 104 M−1; Ksv = 2.6 × 103 M−1). In addition, compounds selected for non-clinical toxicity testing did not show serious signs of toxicity at the dose of 2000 mg/kg in mice; cytotoxic tests performed on leukemic cells (K-562) and its resistant form (K-562 Lucena 1) identified moderate potency for DL-01 and DL-08, with IC50 between 11.45 and 17.32 µM.

Cu(II)-Promoted the Chemical Synthesis of New Azines-Based Naphthalene Scaffold as In Vitro Potent Mushroom Tyrosinase Inhibitors and Evaluation of Their Antiproliferative Activity

Herein, synthesis of new designated azines-based naphthalene scaffold (3a–10) was assisted by CuCl2.2H2O for the first time. Their biological screening manifested that azines 3a, 4, 7, 9, and 10 exhibit effectual mushroom tyrosinase inhibition with IC50 values within the ambit of 3.75–12.36 µM. Mostly, azines 4 and 9 demonstrated about four-fold enhancement in the activity (IC50 = 3.91 ± 0.16, 3.75 ± 0.15 µM, respectively) comparable to the kojic acid (IC50 = 16.86 ± 0.84 µM). Molecular docking of azines 4 and 9 against mushroom tyrosinase (2Y9X) proved the significant rule of isatin moiety (4) in hydrogen bonding, the importance of 4-dimethylamino styryl unit (9) in hydrophobic interactions, and the overall findings confirmed the momentousness of azine group (N–N) and naphthalene scaffold in the interactions with the histidine key residues of the tyrosinase binding pocket. Evaluation of antiproliferative activity indicated that, azine 4 was the most potent one against both MCF-7 and HCT116 with IC50 values of 4.35 ± 0.18 and 2.41 ± 0.12 µM, respectively. Whereas 9 was the most robust azine toward HepG2 with an IC50 value of 2.19 ± 0.12 µM. Exhaustively, azines 4 and 9 could be promising biomedical lead candidates.

Evaluation of Antiproliferative Activity of Lac Dye Fractions against MDA-MB-231 and SiHa Cell Lines.

Laccifer lacca (Kerr) produces a mixture of polyhydroxy anthraquinones (laccaic acid) known as lac dye. Literature suggests that these laccaic acids have a structural resemblance with the anticancer drug Adriamycin (ADR). Hence, they may possess potential anticancer activity. This study was designed to explore the in vitro anticancer activity of the three fractions of lac dye, i.e., chloroform (C), methanol (M), and water (W) fractions, and isolation of constituents from bioactive fraction. SRB (Sulforhodamine B) assay method was employed to evaluate the inhibitory action of all three fractions. However, only methanolic showed promising inhibitory action with GI50 <10; this runs in parallel with Adriamycin inhibition (GI50 <10). Two active constituents of the methanolic extract were isolated using column chromatography and were characterized using UV (UV visible spectrophotometer), IR (Infrared spectroscopy), NMR (nuclear magnetic resonance), and mass spectrometry methods. The final structure of the isolated constituents (laccaic acid D and laccaic acid B) was confirmed by 13C and 2D NMR data. Conclusively, only the methanol fraction (M) showed promising anticancer activity against in vitro MDAMB- 231 and SiHa cell lines compared to the standard adriamycin.

Purification and Identification of Flavonoid Molecules from Rosa setate x Rosa rugosa Waste Extracts and Evaluation of Antioxidant, Antiproliferative and Antimicrobial Activities.

Rosa setate x Rosa rugosa is widely used in the essential oil industry and generates large amounts of waste annually. The purpose of this research is the recycling of bioactive flavonoids from rose waste biomass to develop high-value products. Resin screening and adsorption/desorption dynamic analysis showed that HP20 resin was suitable to purify the flavonoids from R. setate x R. rugosa waste extracts. Under the optimal enrichment process, the product had a 10.7-fold higher purity of flavonoids with a satisfactory recovery of 82.02%. In total, 14 flavonoids were identified in the sample after purification by UHPLC-QTOF-MS. Moreover, the DPPH and ABTS assays revealed that the flavonoids-purified extracts exhibited higher antioxidant activities than the crude extracts. Meanwhile, the purified extracts presented stronger antiproliferative activity against HepG2, Caco-2, MCF-7 and A549 cell lines. The bacteriostatic effects of the purified extracts against four bacteria (Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Staphylococcus epidermidis (S. epidermidis), Pseudomonas aeruginosa (P. aeruginosa)) and yeast (Candida albicans (C. albicans)) were stronger compared with the crude extracts. It was concluded that flavonoids-enriched extracts from R. setate x R. rugosa waste had the potential to be applied in functional food and pharmaceutical industries.

Antiproliferative activity of Brassica nigra seeds extract in liver tissue of mice exposed to phenobarbital

Hepatocellular proliferation is one of the most common causes of hepatocellular carcinoma (HCC), a type of cancer that is widely distributed disease. Hepatocellular carcinoma treatment has numerous barriers, including ineffectiveness, side effects, and drug resistance to currently available treatments. Previous studies showed that a high intake of Brassica vegetables has been associated to a decreased risk of a number of malignancies. The aim of this study is the evaluation of antiproliferative activity of Brassica nigra seeds extract in mice exposed to phenobarbital. Brassica nigra seeds where extracted; phytochemical analysis of the extract was done that including phytochemical screening tests and Gas chromatography-mass spectrometry (GC-MS) analysis. Antiproliferative activity of hydro alcoholic Brassica seeds extract has been studied by 800mg/kg and compare with control group (given normal saline), phenobarbital group (Phenobarbital 75mg/kg) and combination group (Brassica extract 800mg/kg+ Phenobarbital 75mg/kg). The GC-MS analysis revealed the presence of isothiocynate compound. Histologically phenobarbital induced severe hepatocellular proliferation (hyperplasia and hypertrophy), glass ground cytoplasm, while Brassica seeds extract produce improvement in histopathological changes that include mild scattered proliferation picture and eosinophilic cytoplasm. In comparison to phenobarbital group, Combination groups pretreated with Brassica nigra seeds for 14 days and phenobarbital for 7 days caused significant reduction relative liver weight and alanine aminotransferase (ALT) Brassica nigra seeds extract have isothiocynate as main compound it showed antiproliferative action on the liver tissue, implying that it may have a promising effect in minimizing the risk of liver cancer.