Hyperphosphorylated PTEN exerts oncogenic properties.

PTEN is a multifaceted tumor suppressor that is highly sensitive to alterations in expression or function. The PTEN C-tail domain, which is rich in phosphorylation sites, has been implicated in PTEN stability, localization, catalytic activity, and protein interactions, but its role in tumorigenesis remains unclear. To address this, we utilized several mouse strains with nonlethal C-tail mutations. Mice homozygous for a deletion that includes S370, S380, T382 and T383 contain low PTEN levels and hyperactive AKT but are not tumor prone. Analysis of mice containing nonphosphorylatable or phosphomimetic versions of S380, a residue hyperphosphorylated in human gastric cancers, reveal that PTEN stability and ability to inhibit PI3K-AKT depends on dynamic phosphorylation-dephosphorylation of this residue. While phosphomimetic S380 drives neoplastic growth in prostate by promoting nuclear accumulation of ß-catenin, nonphosphorylatable S380 is not tumorigenic. These data suggest that C-tail hyperphosphorylation creates oncogenic PTEN and is a potential target for anti-cancer therapy.

Tumour microenvironment and heterotypic interactions in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is a disease with a survival rate of 9%; this is due to its chemoresistance and the large tumour stroma that occupies most of the tumour mass. It is composed of a large number of cells of the immune system, such as Treg cells, tumour-associated macrophages (TAMs), myeloid suppressor cells (MDCs) and tumour-associated neutrophiles (TANs) that generate an immunosuppressive environment by the release of inflammatory cytokines. Moreover, cancer-associated fibroblast (CAFs) provide a protective coverage that would difficult the access of chemotherapy to the tumour. According to this, new therapies that could remodel this heterogeneous tumour microenvironment, such as adoptive T cell therapies (ACT), immune checkpoint inhibitors (ICI), and CD40 agonists, should be developed for targeting PDA. This review organizes the different cell populations found in the tumour stroma involved in tumour progression in addition to the different therapies that are being studied to counteract the tumour.

ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology.

Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5-KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology.

Senescent cells limit p53 activity via multiple mechanisms to remain viable.

Super-enhancers regulate genes with important functions in processes that are cell type-specific or define cell identity. Mouse embryonic fibroblasts establish 40 senescence-associated super-enhancers regardless of how they become senescent, with 50 activated genes located in the vicinity of these enhancers. Here we show, through gene knockdown and analysis of three core biological properties of senescent cells that a relatively large number of senescence-associated super-enhancer-regulated genes promote survival of senescent mouse embryonic fibroblasts. Of these, Mdm2, Rnase4, and Ang act by suppressing p53-mediated apoptosis through various mechanisms that are also engaged in response to DNA damage. MDM2 and RNASE4 transcription is also elevated in human senescent fibroblasts to restrain p53 and promote survival. These insights identify key survival mechanisms of senescent cells and provide molecular entry points for the development of targeted therapeutics that eliminate senescent cells at sites of pathology.

Current Insights on the Impact of Proteomics in Respiratory Allergies.

Respiratory allergies affect humans worldwide, causing extensive morbidity and mortality. They include allergic rhinitis (AR), asthma, pollen food allergy syndrome (PFAS), aspirin-exacerbated respiratory disease (AERD), and nasal polyps (NPs). The study of respiratory allergic diseases requires new technologies for early and accurate diagnosis and treatment. Omics technologies provide the tools required to investigate DNA, RNA, proteins, and other molecular determinants. These technologies include genomics, transcriptomics, proteomics, and metabolomics. However, proteomics is one of the main approaches to studying allergic disorders' pathophysiology. Proteins are used to indicate normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. In this field, the principal goal of proteomics has been to discover new proteins and use them in precision medicine. Multiple technologies have been applied to proteomics, but that most used for identifying, quantifying, and profiling proteins is mass spectrometry (MS). Over the last few years, proteomics has enabled the establishment of several proteins for diagnosing and treating respiratory allergic diseases.

Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR).

Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis due to its late diagnosis and strong chemoresistance to the current treatments. Therefore, finding new therapeutic targets is an urgent need nowadays. In this study, we report the role of the chromatin remodeler BPTF (Bromodomain PHD Finger Transcription Factor) as a therapeutic target in PDA. BPTF-silencing dramatically reduced cell proliferation and migration in vitro and in vivo in human and mouse PDA cell lines. Moreover, BPTF-silencing reduces the IC50 of gemcitabine in vitro and enhanced its therapeutic effect in vivo. Mechanistically, BPTF is required for c-MYC recruitment to the promoter of ABC-transporters and its downregulation facilitates gemcitabine accumulation in tumour cells, increases DNA damage, and a generates a strong synergistic effect in vivo. We show that BPTF is a therapeutic target in pancreatic ductal adenocarcinoma due to its strong effect on proliferation and in response to gemcitabine.

Senescent cells suppress innate smooth muscle cell repair functions in atherosclerosis.

Senescent cells (SNCs) degenerate the fibrous cap that normally prevents atherogenic plaque rupture, a leading cause of myocardial infarction and stroke. Here we explored the underlying mechanism using pharmacological or transgenic approaches to clear SNCs in the Ldlr -/- mouse model of atherosclerosis. SNC clearance reinforced fully deteriorated fibrous caps in highly advanced lesions, as evidenced by restored vascular smooth muscle cell (VSMC) numbers, elastin content, and overall cap thickness. We found that SNCs inhibit VSMC promigratory phenotype switching in the first interfiber space of the arterial wall directly beneath atherosclerotic plaque, thereby limiting lesion entry of medial VSMCs for fibrous cap assembly or reinforcement. SNCs do so by antagonizing IGF-1 through the secretion of insulin-like growth factor-binding protein 3 (Igfbp3). These data indicate that the intermittent use of senolytic agents or IGFBP-3 inhibition in combination with lipid lowering drugs may provide therapeutic benefit in atherosclerosis.

Transcriptome Analysis Identifies Doublesex and Mab-3 Related Transcription Factor (DMRT3) in Nasal Polyp Epithelial Cells of Patients Suffering from Non-Steroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease (AERD).

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a syndrome characterised by chronic rhinosinusitis, nasal polyps, asthma and aspirin intolerance. An imbalance of eicosanoid metabolism with anover-production of cysteinyl leukotrienes (CysLTs) has been associated with AERD. However, the precise mechanisms underlying AERD are unknown. OBJECTIVE: To establish the transcriptome of the nasal polyp airway epithelial cells derived from AERD patients to discover gene expression patterns in this disease. METHODS: Nasal airway epithelial cells were isolated from 12 AERD polyps and 8 AERD non-polyp nasal mucosa samples as controls from the same subjects. Utilising the Illumina HiSeq 2500 platform, RNA samples were sequenced. Potential gene candidate DMRT3 was selected from the differentially-expressed genes for validation. RESULTS: Comparative transcriptome profiling of nasal epithelial cells was accomplished in AERD. A total of 20 genes had twofold mean regulation expression differences or greater. In addition, 8 genes were upregulated, including doublesex and mab-3 related transcription factor 3 (DMRT3), and 12 genes were downregulated. Differentially regulated genes comprised roles in inflammation, defence and immunity. Metabolic process and embryonic development pathways were significantly enriched. Enzyme-linked immune sorbent assay (ELISA) results of DMRT3 in AERD patients were significantly upregulated compared to controls (p = 0.03). Immunohistochemistry (IHC) of AERD nasal polyps localised DMRT3 and was predominantly released in the airway epithelia. CONCLUSION: Findings suggest that DMRT3 could be potentially involved in nasal polyp development in AERD patients. Furthermore, several genes are downregulated, hinting at the dedifferentiation phenomenon in AERD polyps. However, further studies are imperative to confirm the exact mechanism of polyp formation in AERD patients.

Flow of long chain hydrocarbons through carbon nanotubes (CNTs).

The pressure-driven flow of long-chain hydrocarbons in nanosized pores is important in energy, environmental, biological, and pharmaceutical applications. This paper examines the flow of hexane, heptane, and decane in carbon nanotubes (CNTs) of pore diameters 1-8 nm using molecular dynamic simulations. Enhancement of water flow in CNTs in comparison to rates predicted by continuum models has been well established in the literature. Our work was intended to observe if molecular dynamic simulations of hydrocarbon flow in CNTs produced similar enhancements. We used the OPLS-AA force field to simulate the hydrocarbons and the CNTs. Our simulations predicted the bulk densities of the hydrocarbons to be within 3% of the literature values. Molecular sizes and shapes of the hydrocarbon molecules compared to the pore size create interesting density patterns for smaller sized CNTs. We observed moderate flow enhancements for all the hydrocarbons (1-100) flowing through small-sized CNTs. For very small CNTs the larger hydrocarbons were forced to flow in a cork-screw fashion. As a result of this flow orientation, the larger molecules flowed as effectively (similar enhancements) as the smaller hydrocarbons.

Molecular Alterations in Pancreatic Cancer: Transfer to the Clinic.

Pancreatic ductal adenocarcinoma (PDA) is the most common cancer of the exocrine pancreas and probably the tumor that has benefited the least from clinical progress in the last three decades. A consensus has been reached regarding the histologic classification of the ductal preneoplastic lesions (pancreatic intra-epithelial neoplasia-PanIN) and the molecular alterations associated with them. Mutations in KRAS and inactivation of CDKN2A, SMAD4 and TP53 are among the most prevalent alterations. Next generation sequencing studies are providing a broad picture of the enormous heterogeneity in this tumor type, describing new mutations less prevalent. These studies have also allowed the characterization of different subtypes with prognostic value. However, all this knowledge has not been translated into a clinical progress. Effective preventive and early diagnostic strategies are essential to improve the survival rates. The main challenge is, indeed, to identify new effective drugs. Despite many years of research and its limited success, gemcitabine is still the first line treatment of PDA. New drug combinations and new concepts to improve drug delivery into the tumor, as well as the development of preclinical predictive assays, are being explored and provide optimism and prospects for better therapies.

FoxM1 insufficiency hyperactivates Ect2-RhoA-mDia1 signaling to drive cancer.

FoxM1 activates genes that regulate S-G2-M cell-cycle progression and, when overexpressed, is associated with poor clinical outcome in multiple cancers. Here we identify FoxM1 as a tumor suppressor in mice that, through its N-terminal domain, binds to and inhibits Ect2 to limit the activity of RhoA GTPase and its effector mDia1, a catalyst of cortical actin nucleation. FoxM1 insufficiency impedes centrosome movement through excessive cortical actin polymerization, thereby causing the formation of non-perpendicular mitotic spindles that missegregate chromosomes and drive tumorigenesis in mice. Importantly, low FOXM1 expression correlates with RhoA GTPase hyperactivity in multiple human cancer types, indicating that suppression of the newly discovered Ect2-RhoAmDia1 oncogenic axis by FoxM1 is clinically relevant. Furthermore, by dissecting the domain requirements through which FoxM1 inhibits Ect2 GEF activity, we provide mechanistic insight for the development of pharmacological approaches that target protumorigenic RhoA activity.

Identification of 6-amino-1H-pyrazolo[3,4-d]pyrimidines with in vivo efficacy against visceral leishmaniasis.

Visceral leishmaniasis (VL) affects millions of people across the world, largely in developing nations. It is fatal if left untreated and the current treatments are inadequate. As such, there is an urgent need for new, improved medicines. In this paper, we describe the identification of a 6-amino-N-(piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidine scaffold and its optimization to give compounds which showed efficacy when orally dosed in a mouse model of VL.

Optimisation of a key cross-coupling reaction towards the synthesis of a promising antileishmanial compound.

During the course of a research program aimed at identifying novel antileishmanial compounds, a multi-gram synthesis of N-(trans-4-((4-methoxy-3-((R)-3-methylmorpholino)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)cyclohexyl)-2-methylpropane-1-sulfonamide (( R )-1) was required. This letter describes optimisation of the reaction conditions and protecting group strategy for a key Buchwald-Hartwig coupling, delivering the required quantities of ( R )-1, as well as further compounds in the series.

Ccne1 Overexpression Causes Chromosome Instability in Liver Cells and Liver Tumor Development in Mice.

BACKGROUND & AIMS: The CCNE1 locus, which encodes cyclin E1, is amplified in many types of cancer cells and is activated in hepatocellular carcinomas (HCCs) from patients infected with hepatitis B virus or adeno-associated virus type 2, due to integration of the virus nearby. We investigated cell-cycle and oncogenic effects of cyclin E1 overexpression in tissues of mice. METHODS: We generated mice with doxycycline-inducible expression of Ccne1 (Ccne1T mice) and activated overexpression of cyclin E1 from age 3 weeks onward. At 14 months of age, livers were collected from mice that overexpress cyclin E1 and nontransgenic mice (controls) and analyzed for tumor burden and by histology. Mouse embryonic fibroblasts (MEFs) and hepatocytes from Ccne1T and control mice were analyzed to determine the extent to which cyclin E1 overexpression perturbs S-phase entry, DNA replication, and numbers and structures of chromosomes. Tissues from 4-month-old Ccne1T and control mice (at that age were free of tumors) were analyzed for chromosome alterations, to investigate the mechanisms by which cyclin E1 predisposes hepatocytes to transformation. RESULTS: Ccne1T mice developed more hepatocellular adenomas and HCCs than control mice. Tumors developed only in livers of Ccne1T mice, despite high levels of cyclin E1 in other tissues. Ccne1T MEFs had defects that promoted chromosome missegregation and aneuploidy, including incomplete replication of DNA, centrosome amplification, and formation of nonperpendicular mitotic spindles. Whereas Ccne1T mice accumulated near-diploid aneuploid cells in multiple tissues and organs, polyploidization was observed only in hepatocytes, with losses and gains of whole chromosomes, DNA damage, and oxidative stress. CONCLUSIONS: Livers, but not other tissues of mice with inducible overexpression of cyclin E1, develop tumors. More hepatocytes from the cyclin E1-overexpressing mice were polyploid than from control mice, and had losses or gains of whole chromosomes, DNA damage, and oxidative stress; all of these have been observed in human HCC cells. The increased risk of HCC in patients with hepatitis B virus or adeno-associated virus type 2 infection might involve activation of cyclin E1 and its effects on chromosomes and genomes of liver cells.

Mosaic-variegated aneuploidy syndrome mutation or haploinsufficiency in Cep57 impairs tumor suppression.

A homozygous truncating frameshift mutation in CEP57 (CEP57T/T) has been identified in a subset of mosaic-variegated aneuploidy (MVA) patients; however, the physiological roles of the centrosome-associated protein CEP57 that contribute to disease are unknown. To investigate these, we have generated a mouse model mimicking this disease mutation. Cep57T/T mice died within 24 hours after birth with short, curly tails and severely impaired vertebral ossification. Osteoblasts in lumbosacral vertebrae of Cep57T/T mice were deficient for Fgf2, a Cep57 binding partner implicated in diverse biological processes, including bone formation. Furthermore, a broad spectrum of tissues of Cep57T/T mice had severe aneuploidy at birth, consistent with the MVA patient phenotype. Cep57T/T mouse embryonic fibroblasts and patient-derived skin fibroblasts failed to undergo centrosome maturation in G2 phase, causing premature centriole disjunction, centrosome amplification, aberrant spindle formation, and high rates of chromosome missegregation. Mice heterozygous for the truncating frameshift mutation or a Cep57-null allele were overtly indistinguishable from WT mice despite reduced Cep57 protein levels, yet prone to aneuploidization and cancer, with tumors lacking evidence for loss of heterozygosity. This study identifies Cep57 as a haploinsufficient tumor suppressor with biologically diverse roles in centrosome maturation and Fgf2-mediated bone formation.

Frecuencia del síndrome metabólico y factores de riesgo en adultos con y sin diabetes mellitus e hipertensión arterial / Frequency of metabolic syndrome and risk factors in adults with and without diabetes mellitus and arterial hypertension

RESUMEN Objetivo Determinar la frecuencia y factores de riesgo para Síndrome Metabólico (SM) en adultos con Diabetes mellitus, hipertensión arterial y sin diabetes-hipertensión. Material y Métodos Se realizó un estudio transversal analítico en derechohabientes de ambos sexos y mayores de 20 años de los servicios de consulta externa del HGZ No. 1 IMSS Colima, México. Las variables estudiadas fueron edad, IMC, diámetro de la cintura, grado de escolaridad, estado socioeconómico, grado de actividad física, tabaquismo, antecedentes familiares para diabetes e hipertensión arterial (HTA) y parámetros bioquímicos como glucosa, colesterol HDL, triglicéridos. Resultados Se estudiaron 417 pacientes (170 hombres y 247 mujeres), con un promedio de edad 53,2 ± 13,4 años (intervalo 20 a 86 años). La frecuencia global del SM fue del 52,3 % (56 % mujeres y 46,4 % hombres). Mientras que la frecuencia del SM fue de 50 % en DM2, 42% en HTA, 80 % DM2 + HTA y 28,2 % sin DM o HTA. La frecuencia del tabaquismo fue del 27,8 % y fue un factor de riesgo importante para la totalidad de pacientes con SM, en DM2 y en DM2+HAT. Conclusiones La frecuencia del SM en adultos fue del 52,3 %, las mujeres fueron más afectadas y el tabaquismo fue el factor de riesgo más importante.(AU)

ABSTRACT Objective Determinate the frequency and the risk factors for Metabolic Syndrome in adults with diabetes mellitus, Hypertension and without Diabetes- Hypertension. Materials and Methods We realized a cross-sectional study in patients of both sexes and older than 20 years of the "Hospital General de Zona 1 IMSS" in Colima, Mexico. The variables studied were: age, BMI, waist circumference, cigarette smoking, and family history of diabetes and hypertension, and biochemical parameters, such as glucose, HDL cholesterol and triglycerides. Results A total of 417 persons were enrolled (170 men and 247 women), with an age average of 53.2 ± 13.4 years (age range, 20 to 86 years). The global frequency of the metabolic syndrome was 52.3 % (56 % in women and 46.4 % in men). While the MS frequency was 50 % in DM2, 42 % in hypertension, 80 % in DM2+hypertension and 28.2 % without DM2 and hypertension. The cigarette smoking frequency was 27.8 %, and it was an important risk factor for the totally of patients with MS, in DM2 and in DM2+hypertension. Conclusions The frequency of MS in adults was 52.3 %, women were the most affected, and cigarette smoking was the most important risk factor.(AU)

[Frequency of metabolic syndrome and risk factors in adults with and without diabetes mellitus and arterial hypertension]. / Frecuencia del síndrome metabólico y factores de riesgo en adultos con y sin diabetes mellitus e hipertensión arterial.

OBJECTIVE: Determinate the frequency and the risk factors for Metabolic Syndrome in adults with diabetes mellitus, Hypertension and without Diabetes- Hypertension. MATERIALS AND METHODS: We realized a cross-sectional study in patients of both sexes and older than 20 years of the "Hospital General de Zona 1 IMSS" in Colima, Mexico. The variables studied were: age, BMI, waist circumference, cigarette smoking, and family history of diabetes and hypertension, and biochemical parameters, such as glucose, HDL cholesterol and triglycerides. RESULTS: A total of 417 persons were enrolled (170 men and 247 women), with an age average of 53.2 ± 13.4 years (age range, 20 to 86 years). The global frequency of the metabolic syndrome was 52.3 % (56 % in women and 46.4 % in men). While the MS frequency was 50 % in DM2, 42 % in hypertension, 80 % in DM2+hypertension and 28.2 % without DM2 and hypertension. The cigarette smoking frequency was 27.8 %, and it was an important risk factor for the totally of patients with MS, in DM2 and in DM2+hypertension. CONCLUSIONS: The frequency of MS in adults was 52.3 %, women were the most affected, and cigarette smoking was the most important risk factor.

OBJETIVO: Determinar la frecuencia y factores de riesgo para Síndrome Metabólico (SM) en adultos con Diabetes mellitus, hipertensión arterial y sin diabetes-hipertensión. MATERIAL Y MÉTODOS: Se realizó un estudio transversal analítico en derechohabientes de ambos sexos y mayores de 20 años de los servicios de consulta externa del HGZ No. 1 IMSS Colima, México. Las variables estudiadas fueron edad, IMC, diámetro de la cintura, grado de escolaridad, estado socioeconómico, grado de actividad física, tabaquismo, antecedentes familiares para diabetes e hipertensión arterial (HTA) y parámetros bioquímicos como glucosa, colesterol HDL, triglicéridos. RESULTADOS: Se estudiaron 417 pacientes (170 hombres y 247 mujeres), con un promedio de edad 53,2 ± 13,4 años (intervalo 20 a 86 años). La frecuencia global del SM fue del 52,3 % (56 % mujeres y 46,4 % hombres). Mientras que la frecuencia del SM fue de 50 % en DM2, 42% en HTA, 80 % DM2 + HTA y 28,2 % sin DM o HTA. La frecuencia del tabaquismo fue del 27,8 % y fue un factor de riesgo importante para la totalidad de pacientes con SM, en DM2 y en DM2+HAT. CONCLUSIONES: La frecuencia del SM en adultos fue del 52,3 %, las mujeres fueron más afectadas y el tabaquismo fue el factor de riesgo más importante.

Adverse drug reactions in internal medicine units and associated risk factors.

OBJECTIVES: This study was designed to assess the prevalence of adverse drug reactions (ADRs) in the internal medicine wards of two teaching hospitals, identify the most common ADRs, the principal medications involved, and determine the risk factors implicated in the occurrence of such ADRs. METHODS: All admissions over 10 weeks were followed prospectively using an intensive drug surveillance method to identify ADRs. Clinical laboratory data, the drug prescribed, and ADRs were taken into consideration. Status of nutrition, liver and kidney function at admission, and ADR time were determined. In order to assess drug interactions a software package was used. RESULTS: A total of 405 patients were evaluated, 126 patients (31%) had 128 ADRs, 122 ADRs occurred during hospitalization. Two ADR-related deaths were observed during the study. Reactions affecting the gastrointestinal tract, skin, and hematological system were among the most frequent ADRs. For ADRs observed during admission predictors of its occurrence in a multivariate regression model were: OR (95% CI); more than 12 days' hospitalization: 2.11(1.27-3.47), any drug interaction: 9.33 (5.12-17) and acute change in estimated glomerular filtration rate over admission >20%: 2.46 (1.45-4.2). Worsening of renal function or drug interaction was observed in nine of the ten ADRs. Age, sex, nutrition, and number of drugs used were not related to ADRs. CONCLUSION: A significant prevalence of ADRs was found among hospitalized patients. Duration of hospital admission, changes in renal status during hospitalization and drug interactions seem to be important risk factors for ADRs.

Synthesis, structure and biological activities of cobalt(II) and zinc(II) coordination compounds with 2-benzimidazole derivatives.

In this work we present the synthesis, structural and spectroscopic characterisation of a series of cobalt(II) and zinc(II) coordination compounds with benzimidazole (bz) and its 2-benzimidazole derivatives: 2-aminobenzimidazole (2ab), albendazole (abz) and tris(2-benzimidazolylmethyl)amine (ntb). The compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus, Micrococcus luteus, Salmonella typhi, Pseudomonas aeruginosa, Escherichia coli and Proteus vulgaris. Their cytotoxic activity was also evaluated using human cancer lines, HeLa, HCT-15 and SKLU-1. The halide tetrahedral compounds [Co(bz)2Br2] 3, [Zn(2ab)2Cl2].0.5H2O 11, [Co(abz)Cl2(H2O)].3H2O 14, [Co(abz)Br2(H2O)] 15, [Zn(abz)Cl2(H2O)].3H2O 17 and [Zn(abz)Br2(H2O)].H2O 18 displayed similar minimal inhibition concentration (MIC) values against Micrococcus luteus and Escherichia coli, comparable to those of amoxicillin and chloramphenicol. Additionally, 11 showed a wide range of activity towards Gram(+) and Gram(-) microorganisms. The tetradentate ntb and its trigonal bipyramidal cobalt(II) and zinc(II) compounds were active, regardless of the anion present in the complex. Compound [Co(abz)Cl2(H2O)].3H2O 14 showed promising activity in HeLa cells, while [Co(ntb)Br]Br.H2O 21 inhibited Hela and HCT-15 cell lines.