Human Breast Carcinoma Cell Line Research Articles

The effect of hesperidin and luteolin isolated from Eriocephalus africanus on apoptosis, cell cycle and miRNA expression in MCF-7

This study investigates the molecular mechanisms underlying the anticancer activity of hesperidin and luteolin, isolated from Eriocephalus africanus, in the human breast carcinoma cell line (MCF-7). The viability of MCF-7 cells, upon treatment with hesperidin and luteolin, was evaluated using the 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay; apoptotic activity and effect on cell cycle progression were analysed by flow cytometry; effect on expression of key apoptotic regulatory genes (caspase-3, -8, -9, Bcl-2 and Bax) and apoptotic microRNAs (-16, -21 and -34a) were evaluated using quantitative real-time PCR. Hesperidin and luteolin reduced cell viability in a dose and time-dependent manner, caused a significant accumulation of apoptotic cells into the G0/G1 and sub-G1 cell cycle phases, induced apoptosis through the intrinsic and extrinsic pathways, down-regulated anti-apoptotic, Bcl-2, and upregulated pro-apoptotic, Bax. In addition, hesperidin and luteolin significantly downregulated the expression of miR-21 and upregulated that of miR-16 and -34a in MCF-7. Spearman`s rank analysis revealed a positive correlation between Bcl-2 and miR-21 and negative correlation between Bcl-2, miR-16 and -34a. Findings from this study provide new evidence on the molecular basis of the anticancer activity of luteolin and hesperidin in breast cancer cell lines. Communicated by Ramaswamy H. Sarma

DFT, anticancer, antioxidant and molecular docking investigations of some ternary Ni(II) complexes with 2-[(E)-[4-(dimethylamino)phenyl]methyleneamino]phenol

The biological activities of some ternary nickel complexes with a Schiff base obtained from 4-dimethylaminobenzaldehyde and 2-aminophenol have been reported. The Schiff base (HL1) acts as a primary ligand whereas, anthranilic acid (HL2), 2-nitroaniline (HL3), alanine (HL4) and histidine (HL5) act as secondary ligand or co-ligand. The anticancer activity of these compounds was studied against human colon carcinoma (HCT-116), human hepatocellular liver carcinoma (HEPG-2) and human breast carcinoma (MCF-7) cell lines. As per the results, the compounds were active against the cell lines. The antioxidant activity of the same compounds was evaluated using DPPH (1,1-diphenyl-2-picryl-hydrazyl) radical scavenging and compared with ascorbic acid. The DFT computations for these compounds were made to understand the bonding mode by a GAUSSIAN 09 program. Moreover, a docking analysis using Autodock 4.2 software package was carried out against the tyrosine kinase receptor (PDB ID: 1M17). In addition, QSAR investigation was also performed to understand the biological potency of the ligand.

Preparation, characterization and evaluation of cytotoxic activity of Tamoxifen bound liposomes against breast cancer cell line

The goal of this study was to determine whether neutrally or positively charged liposomes encapsulated with tamoxifen could inhibit the proliferation of human breast cancer MCF-7 cell proliferation compared to free tamoxifen by estimating the potential effects of these complexes on the cell death of human breast carcinoma (MCF-7) cell lines. The formulated tamoxifen liposomal conjugate was characterized by analytical techniques to determine its size, size-distribution, thermotropic changes and conformational changes along with possible cytotoxicity towards MCF-7 (breast cancer cell line) in Vitro. The mean particle diameter was estimated to be 64.70±49.75 nm, 73.72±23.8 nm and 119±54.7 nm for blank liposomes, neutral and positively charged liposomes bound tamoxifen, respectively. As tamoxifen is introduced into positive liposomes, it results in noticeable broadening and shift to lower temperature at 135 C compared to the main characteristic endothermic peak (Tm) of pure liposomes that exists at 140C, while the introduction of tamoxifen into neutral liposomes contributes to the disappearance of the main endothermic peak of pure liposomes. FTIR analysis revealed structure changes in vesicles after tamoxifen was incorporated into liposomes. The IC50 value for tamoxifen in the cytotoxic assay with MCF-7 treated cells was 0.34 μg/ml, while tamoxifen-loaded neutrally or positively charged liposomes showed an increase of IC50 value to 119.62 and 101.23 µg /ml, respectively. Current data suggests a new treatment regimen in where free tamoxifen is substituted with liposomal tamoxifen to improve anticancer activity against MCF-7 cancer cell lines.

1,2,4-triazole-derived N-heterocyclic carbene complexes of platinum(II) as catalysts for hydroamination reactions and active anticancer agents

A series of five platinum(II) complexes of 1,2,4-triazole derived N-heterocylcic carbenes (R-tazy) with generic formula cis-[PtCl2(R-tazy)(DMSO)] (DMSO = dimethyl sulfoxide) have been successfully synthesized. The complexes feature the carbenes with the same benzyl wingtip, but are differed by their N-4 substituent (R = isopropyl (1), cyclohexyl (2), phenyl (3), mesityl (4) and 2,6-diisopropylphenyl (5)). The two new compounds 1 and 2 were characterized by means of multinuclear (1H, 13C{1H}) magnetic resonance spectroscopy, mass spectrometry, elemental analysis and single crystal X-ray diffraction (for 2). The hindered rotations of the benzyl and κ-S-dimethyl sulfoxide were elucidated using NMR spectroscopy and rationalized with density functional theory (DFT) calculation. Notably, the five complexes were found active catalysts for intermolecular hydroamination of phenylacetylene using aromatic amines in the presence of silver(I) triflate additive. In addition, all the five complexes display high cytotoxicity toward human carcinoma in the mouth (KB), human breast carcinoma (MCF-7) and human colorectal carcinoma (HT-29) cell lines with IC50 concentration in the 3.0 ± 0.4–14.3 ± 1.3 μM range. Interestingly, compound 1 and 3 display lower cytotoxicity toward non-cancerous human embryonic kidney cell (HEK-293A).

Novel Anticancer NHC*-Gold(I) Complexes Inspired by Lepidiline A.

N-Heterocyclic carbene gold(I) complexes derived from 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene (NHC*) represent a promising class of anticancer drugs. Complexes of the type NHC*-Au-L (L = Br−, I−, C≡C-R) and [NHC*-Au-L]+ (L = NHC*, PPh3) have been synthesised. The X-ray crystal structures of all gold(I) complexes are presented; aurophilic interactions were observed in five of the complexes. The anticancer activity was assessed via MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-based proliferation assays against the human colon carcinoma cell line HCT-116wt and the multidrug-resistant human breast carcinoma cell line MCF-7topo. Most complexes showed good cytotoxicity with IC50 values in the low micromolar range, while excellent sub-micromolar activity was observed for 2c, 3a and 3b. Generally, the activity of the ligands studied was as follows: carbene > phosphine > alkyne > halide, with an exception for the highly active iodido derivative 2c.

Nucleosomes effectively shield DNA from radiation damage in living cells.

Eukaryotic DNA is organized in nucleosomes, which package DNA and regulate its accessibility to transcription, replication, recombination and repair. Here, we show that in living cells nucleosomes protect DNA from high-energy radiation and reactive oxygen species. We combined sequence-based methods (ATAC-seq and BLISS) to determine the position of both nucleosomes and double strand breaks (DSBs) in the genome of nucleosome-rich malignant mesothelioma cells, and of the same cells partially depleted of nucleosomes. The results were replicated in the human MCF-7 breast carcinoma cell line. We found that, for each genomic sequence, the probability of DSB formation is directly proportional to the fraction of time it is nucleosome-free; DSBs accumulate distal from the nucleosome dyad axis. Nucleosome free regions and promoters of actively transcribed genes are more sensitive to DSB formation, and consequently to mutation. We argue that this may be true for a variety of chemical and physical DNA damaging agents.

Synthesis, Characterization, Theoretical Studies, and Antimicrobial/Antitumor Potencies of Salen and Salen/Imidazole Complexes of Co (II), Ni (II), Cu (II), Cd (II), Al (III) and La (III)

Although salens and imidazoles are well‐studied motifs among bioactive and therapeutic agents, their properties when combined in transition metal complexes are not well developed. To explore the structure/reactivity of this class of compounds, a salen‐based ligand, namely (2,2′‐{1,2‐ethanediylbis[nitrilo(E)methylylidene]}diphenol, S), and its binary (MS) and ternary (MSI) complexes (I = imidazole; M = Co (II), Ni (II), Cu (II), Cd (II), Al (III), and La (III)) have been synthesized and fully characterized by standard physicochemical and theoretical methods. Evidence from structural analysis tools along with DFT modeling revealed an unusual monobasic tridentate salen binding mode, involving the phenolic oxygen, the nitrogen of the azomethine group, and NH group formed via phenol‐to‐cyclohexadienone tautomerization, giving rise to a general molecular formula of MSI complexes as [M(S)(I)2(Cl)] for M (II) = Co, Ni, Cu and Cd or [M(S)(I)(Cl)2] for M (III) = Al and La, respectively. The antimicrobial activities of S, MS, and MSI were screened against several bacterial and fungal strains. Of all tested complexes, CdS and CuSI were the most effective antimicrobials, giving larger inhibition zones than the reference antibiotics. The antimicrobial efficacy for the MS complexes follows the order: CdS > gentamicin > CuS > NiS > CoS > LaS > AlS > S, whereas MSI complex, potencies are ordered as CuSI > gentamicin > CdSI >NiSI > CoSI > LaSI > AlSI > S. In vitro cytotoxicity screening of MSI complexes disclosed that both CuSI and CdSI exhibited higher activity against human liver (Hep‐G2) and breast (MDA‐MB231) carcinoma cell lines than the reference (cisplatin) drug. The satisfactory bioactivities observed for several of these compounds supports the underlying design idea for combining important bioactive motifs for possible therapeutic benefit.

Bioactive fluorenes. Part III: 2,7-dichloro-9H-fluorene-based thiazolidinone and azetidinone analogues as anticancer and antimicrobial against multidrug resistant strains agents

BackgroundThiazoles, thiazolidinones and azetidinones are highly ranked amongst natural and synthetic heterocyclic derivatives due to their great pharmaceutical potential.ResultsNew thiazolidinone and azetidinone class of bioactive agents based on 4-(2,7-dichloro-9H-fluoren-4-yl)thiazole moiety have been successfully synthesized. 4-(2,7-dichloro-9H-fluoren-4-yl)thiazol-2-amine was synthesized and allowed to react with various aryl/heteroaryl aldehydes to afford the corresponding Schiff base intermediates. The target thiazolidinone and azetidinone analogues have derived from Schiff bases by their reactions with thioglycolic acid and chloroacetyl chloride, respectively. The newly synthesized compounds were then evaluated for their antimicrobial activity against some multidrug resistant strains and examined for cytotoxic activity against normal lung fibroblast (WI-38), human lung carcinoma (A549), and human breast carcinoma (MDA-MB-231) cell lines to develop a novel class of fluorene-based bioactive agents. The mode of action and the binding interaction of the synthesized compound with the active sites of dihydrofolate reductase enzyme were well identified by fluorescence-activated cell sorting (FACS) analysis and molecular docking study.ConclusionSome of the synthesized compounds showed remarkable activity against A-549 and MDA-MB-231 when compared to Taxol, which was used as a reference drug. 2,7-dichloro-9H-fluorene-based azetidinones are more efficient as antimicrobial and anticancer agents compared to dichloro-9H-fluorene-based thiazolidinones derivatives.

Chemical profile, antiproliferative, antioxidant and enzyme inhibition activities of Ocimum basilicum L. and Pulicaria undulata (L.) C.A. Mey. grown in Sudan

In the present study, essential oils extracted from the leafy stems of Ocimum basilicum (Family Lamiaceae) and Pulicaria undulata (Family Asteraceae) were investigated for their chemical profiles and biological activity including antioxidant, antiproliferative and enzyme inhibition activities. The chemical composition of essential oil was determined using Gas Chromatography-Mass Spectrometry. The antioxidant capacity was tested by scavenging of free radicals, reduction potential, chelating ability on ferrous ions and phosphomolybdenum assays. Cell viability was evaluated on human breast carcinoma (MCF7) and human colon adenocarcinoma (HT29 and HCT116) cell lines. Enzymatic activity was evaluated against α-glucosidase, α-amylase, acetylcholinesterase, butyrylcholinesterase, and tyrosinase. Based on the results obtained, in silico studies was performed to identify potential inhibitor of tyrosinase activity. Results showed that oil of O. basilicum was predominantly composed of methyl chavicol (51.9%) followed by linalool (20.0%). Oil of P. undulata was represented by oxygenated monoterpenes (96.9%) with carvotanacetone (92.1%) as the main molecule. Both oils exerted antioxidant activities with oil from P. undulata exerted significant (p<0.05) higher scavenging activity (20.92±0.05DPPH and 62.36±0.25ABTS mg trolox equivalents (TEs)/g) while that obtained from O. basillicum showed significant (p<0.05) higher total antioxidant activity (16.72±0.95 mmol TEs/g), ion reducing power (86.30±2.80FRAP and 115.31±2.03CUPRAC mg TEs/g) and metal chelating ability (21.08±3.45 mg disodium edetate equivalents /g). Both oils showed considerable tyrosinase and α-amylase inhibition activity while only oil of P. undulata displayed acetylcholinesterase (0.95 ± 0.06 mg galanthamine equivalents (GALAEs)/g), butyrylcholinesterase (1.19 ± 0.13 mg GALAEs/g) and α-glucosidase (32.59 ± 0.20 mg acarbose equivalents (ACAEs)/g) inhibition capacity. Both oils showed good anti-proliferative activity towards the three cell lines with higher activity observed from that of O. basillicum (2.8–3.3 µg/mL). In silico studies suggested that methyl chavicol represent a potential inhibitor of tyrosinase activity. In conclusion, the two oils show promise as natural agents with functional properties for food, cosmetics, and pharmaceutical industries.

Paratrimerin I, cytotoxic acridone alkaloid from the roots of Paramignya trimera

Bioactivity-guided fractionation of the CHCl3-soluble extract of the roots of Paramignya trimera was carried out to obtain a new acridone alkaloid, paratrimerin I. Its structure was elucidated based on NMR spectroscopic data interpretation. Paratrimerin I showed noteworthy cytotoxicity against the HepG2 human hepatocellular and MCF-7 human breast carcinoma cell lines, with the submicromolar IC50 values of 0.43 and 0.26 µM, respectively. The N-methyl, C-4 methoxy, and C-5 hydroxy groups in the acridone skeleton can be proposed as a structural feature for good cytotoxicity.

Cytotoxic Activity of Christia vespertilionis Root and Leaf Extracts and Fractions against Breast Cancer Cell Lines.

Christia vespertilionis, commonly known as ‘Daun Rerama’, has recently garnered attention from numerous sources in Malaysia as an alternative treatment. Its herbal decoction was believed to show anti-inflammatory and anti-cancer effects. The present study investigated the cytotoxicity of the extract of root and leaf of C. vespertilionis. The plant parts were successively extracted using the solvent maceration method. The most active extract was further fractionated to afford F1–F8. The cytotoxic effects were determined using MTT assay against human breast carcinoma cell lines (MCF-7 and MDA-MB-231). The total phenolic content (TPC) of the extracts were determined. The antioxidant properties of the extract were also studied using DPPH and β-carotene bleaching assays. The ethyl acetate root extract demonstrated selective cytotoxicity especially against MDA-MB-231 with the highest TPC and antioxidant properties compared to others (p < 0.05). The TPC and antioxidant results suggest the contribution of phenolic compounds toward its antioxidant strength leading to significant cytotoxicity. F3 showed potent cytotoxic effects while F4 showed better antioxidative strength compared to others (p < 0.05). Qualitative phytochemical screening of the most active fraction, F3, suggested the presence of flavonoids, coumarins and quinones to be responsible toward the cytotoxicity. The study showed the root extracts of C. vespertilionis to possess notable anti-breast cancer effects.

New Derivatives from Microbial Transformation of ent-Kaur-16-en-19-oic Acid by Cunninghamella echinulata.

Biotransformation of ent-kaur-16-en-19-oic acid using fungus Cunninghamella echinulata resulted in two novel hydroxylated metabolites together with five known compounds. Their structures were elucidated by means of extensive NMR and HR-ESI-MS data analysis. The eight compounds were measured for their cytotoxicity against the human breast carcinoma (MCF-7) and human hepatoblastoma (HepG-2) cell lines. Seven compounds showed no cytotoxicity to the two cell lines. One compound displayed moderate cytotoxicity against HepG-2 and MCF-7 with the IC50 values of 12.6 and 27.1 μM, respectively.

Structurally different domains embedded half-sandwich arene Ru(II) complex: DNA/HSA binding and cytotoxic studies

In this investigation, we have designed and synthesized a new Ru(II)-arene complex with triarylamine thiosemicarbazone hybrid ligand to explore its cytotoxicity. The ligand and the complex were well characterized by spectroscopic techniques. From the single-crystal X-ray crystallography, the molecular structure of the ligand was confirmed to be monoclinic lattice with C12/C1 space group symmetry. X-ray photoelectron spectroscopy(XPS) studies ensured that ruthenium is in +2 oxidation state. The synthesized Ru(II)-arene complex was thoroughly investigated for the in vitro activity against human breast carcinoma (MCF-7), human colon carcinoma (COLO 205), human neuroblastoma (IMR-32), murine microphage (Raw 264.7) and embryonic kidney (HEK 293) using MTT assay. The interaction of the Ru(II)-arene complex with DNA/protein was also explored by absorption and emission spectral methods. This investigation highlights the role of hybrid ligand and its Ru(II) complex toward high cytotoxicity in vitro. The complex has high cytotoxic effect with IC50 value of 5.18 ± 1.128 µM toward human breast carcinoma cell line.

A combinatorial approach involving E. coli cytosine deaminase and 5-fluorocytosine-nanoparticles as an enzyme-prodrug therapeutic method for highly substrate selective in situ generation of 5-fluorouracil

Enzyme-prodrug combination is a recognized therapeutic strategy for the treatment of cancer cells. Cytosine deaminases (CD) are non-mammalian proteins perceived to convert the prodrug 5-fluorocytosine (5-FC), into the active antitumor agent 5-fluorouracil (5-FU). In this study, we have synthesized 5-FC as well as 5-FU loaded chitosan-silver nanoparticles in a green synthesis approach, with high yield. The size of the nanoparticles was ascertained to be below 25 nm, thus proficient in penetrating cells. Investigation in human breast carcinoma cell line MDA-MB-468 manifested potent cytotoxicity for 5-FU nanoparticles as compared to the prodrug, 5-FC nanoparticles. E. coli CD (ECD) effectively hydrolyzes 5-FC into 5-FU but was inert to silver nanoparticles as well as 5-FU loaded nanoparticles.

Pollen Bee Aqueous Extract-Based Synthesis of Silver Nanoparticles and Evaluation of Their Anti-Cancer and Anti-Bacterial Activities

Bee pollens are rich source of essential amino acids and are often considered as complete food for human beings. Herein, we exploited the potential reducing abilities of Bee pollens extract for the eco-friendly preparation of silver nanoparticles (AgNPs-G). The resulting NPs were characterized using a combination of microscopic and spectroscopic techniques. The analyses confirm the formation of spherical Ag NPs. AgNPs-G obtained from the aqueous extract of bee pollens was used to study their antibacterial properties against Gram-positive and Gram-negative microbes using the Minimum Inhibitory Concentration 50 (MIC50) method. The antibacterial properties of AgNPs-G were compared to the properties of chemically synthesized Ag NPs (AgNPs-C) using sodium borohydride as a reducing agent. The green synthesized nanoparticles (AgNPs-G) exhibited a better antibacterial activity against most of the studied strains when compared to the chemically synthesized Ag NPs (AgNPs-C). In addition, the anti-cancer activity of Ag NPs was also studied against human liver and breast carcinoma cell lines by applying MTT-assay. The Ag NPs demonstrated considerable anticancer activity against the studied cell lines and exhibited high IC50 values in both MCF-7 and HepG2 cell lines.

Bioactive Fluorenes. Part II. Unprecedented biologically active thiazole derivatives based-2,7-dichlorofluorene as competent DHFR inhibitors: Design, synthesis, and molecular docking approaches

In this study, a new series of (4-(2,7-dichloro-9H-fluoren-4-yl)thiazol-yl)acetamide derivatives was synthesized, and the new heterocycles were completely characterized, evaluated for their antimicrobial activity, and screened for cytotoxic activity against human lung carcinoma (A-549) and human breast carcinoma (MCF-7) cell lines. A molecular docking study was undertaken to identify the possible mode of action of the synthesized compounds, which suggested binding interactions with the dihydrofolate reductase (DHFR) active sites.Most of the synthesized compounds displayed meaningful activity against A-549 and MCF-7 cell lines when compared to 5-fluorouracil (5-FU), which was used as a reference drug. Furthermore, some of the prepared compounds exhibited potent antibacterial and antifungal activities. The highly pronounced biological activities of the compounds under investigation offer such species as promising future drug prospects which may find applications in the fields of biological and medicinal sciences.

Design, synthesis and anticancer activity of novel valproic acid conjugates with improved histone deacetylase (HDAC) inhibitory activity

Twenty-five valproic acid conjugates have been designed and synthesized. All target compounds were explored for their in vitro anti-proliferative activities using the MTT-based assay against four human cancer cell lines includingliver (HePG2), colon (HCT116), breast (MCF7) and cervical (HeLa) carcinoma cell lines. Out of six valproic acid-amino acid conjugates 2a-f. Only cysteine containing conjugate 2f showed the significant activity (IC50 9.10µM against HePG2 and 6.81µM against HCT116). However conjugate 2j showed broad-spectrum antitumor activity against all cell lines tested. In addition, conjugates 4j and 4k which contains phenyl hydrazide and hydroxamic acid group, respectively, also showed broad spectrum activity. Furthermore, six compounds were screened for HDAC 1-9 isozymes inhibitory activities. Compounds 2j, 4j and 4k manifested a higher inhibitory activity more than valproic acid but less than SAHA. In addition, the in vivo antitumor screening of 2j, 4j and 4k was done and the results have shown that 2j, 4j and 4k, particularly 4j, showed a significant decrease in tumor size and presented a considerable decrease in viable EAC count. Docking study of selectedcompound 4j revealed that it can bind nicely to the binding pocket of HDAC 1, 2, 3, 4 and HDAC 8. The results suggest that compounds 2j, 4j and 4k, particularly 4j, may be promising lead candidates for the development of novel targeted anti-tumor drug potentially via inhibiting HDACs.

Tailoring of novel biologically active molecules based on N4-substituted sulfonamides bearing thiazole moiety exhibiting unique multi-addressable biological potentials

Nowadays, the growth of drug-resistant microbial strains (MDRs) is a serious public health threat worldwide. Moreover, tens of millions of people are annually diagnosed with cancer worldwide, and more than half of patients ultimately die. In the present study, a new series of 2-(4-substituted-thiazol-2-ylamino)acetamides and N-(4-substituted-thiazol-2-yl)acetamides incorporating sulfonamide moieties were designed, synthesized, well-characterized and successfully evaluated for their antimicrobial activity against multidrug resistant strains and screened for cytotoxic activity against normal lung fibroblast (WI-38), human lung carcinoma (A549), and human breast carcinoma (MDA-MB-231) cell lines. Fluorescence-activated cell sorting (FACS) analysis and molecular modeling study were performed to identify the mode of action of the novel synthesized compounds and their binding interactions with the active sites of dihydrofolate reductase enzyme (DHFR).

Bersavine: A Novel Bisbenzylisoquinoline Alkaloidwith Cytotoxic, Antiproliferative and Apoptosis-Inducing Effects on Human Leukemic Cells.

Bersavine is the new bisbenzylisoquinoline alkaloid isolated from the Berberis vulgaris L. (Berberidaceae) plant. The results of cytotoxicity screening 48 h post-treatment showed that bersavine considerably inhibits the proliferation and viability of leukemic (Jurkat, MOLT-4), colon (HT-29), cervix (HeLa) and breast (MCF-7) cancer cells with IC50 values ranging from 8.1 to 11 µM. The viability and proliferation of leukemic Jurkat and MOLT-4 cells were decreased after bersavine treatment in a time- and dose-dependent manner. Bersavine manifested concentration-dependent antiproliferative activity in human lung, breast, ovarian and hepatocellular carcinoma cell lines using a xCELLigence assay. Significantly higher percentages of MOLT-4 cells exposed to bersavine at 20 µM for 24 h were arrested in the G1 phase of the cell cycle using the flow cytometry method. The higher percentage of apoptotic cells was measured after 24 h of bersavine treatment. The upregulation of p53 phosphorylated on Ser392 was detected during the progression of MOLT-4 cell apoptosis. Mechanistically, bersavine-induced apoptosis is an effect of increased activity of caspases, while reduced proliferation seems dependent on increased Chk1 Ser345 phosphorylation and decreased Rb Ser807/811 phosphorylation in human leukemic cells.

Synthesis, Characterization, Stability and Cytotoxic Evaluation of Novel Titanium(IV) Complexes of 8-Hydroxyquinoline and 2-Hydroxy-N-phenylbenzylamine Derivatives

A new class of moisture stable heteroleptic titanium(IV) complexes, synthesized from 8-hydroxyquinoline of the type [(Q)2Ti(2-O-5-X-C6H3CH2NC6H4R] (3a-j), was prepared by reacting the antecedent molecule [(Q2)Ti(OiPr)2] (2) with various 2-hydroxy-N-phenyl-benzylamine analogues in 1:1 molar ratios in dry toluene (where, HQ = 8-hydroxyquinoline; iPr = isopropyl; R = H, 4-CH3, 4-OCH3, 2-Cl, 4-Cl, 2-Br, 4-Br; X= H, Br). Moisture sensitive study disclosed that these new metal complexes were unreacted for 72 h. Mass spectral data were employed for proving the mono-nuclearity of the new derivatives. Thermal decomposition pattern of the new derivatives was explained by thermogravimetric analyses. Elemental analyses data are in concordance with their expected values. The hexa-coordinated way of titanium-ligand linkage is further proved through NMR, FTIR, and UV-visible spectral studies. The cytotoxic efficiency of new complexes was tested against MDA-MB-231 human breast carcinoma cell line. Complex 3a exhibited the highest cytotoxic potential of 0.039 μM in comparison to all its analogues of this series by employing cisplatin as the standard