Catalytic olefin epoxidation with cyclopentadienyl-molybdenum complexes in room temperature ionic liquids

Complexes of the type (η⁵-C₅R₅)Mo(CO)₃X (X = Me, Cl; R = H, Me), being efficient homogeneous catalysts for the epoxidation of olefins, have been examined for their catalytic performance at 55 °C in systems containing room temperature ionic liquids (RTILs) of composition [BMIM]NTf₂, [BMIM]PF₆, [C₈MIM]PF₆ and [BMIM]BF₄. The catalytic performance for cyclooctene epoxidation depends strongly on the water content of the system, the catalyst solubility in the RTIL, and the reaction behaviour of the RTIL under the applied reaction conditions. The catalysts can be recycled without significant loss of activity when a reaction system containing [BMIM]NTf₂ and [BMIM]PF₆ in a 4:1 relationship is used. High proportions of [BMIM]PF₆ lead to a ring opening reaction (diol formation), due to HF formation and the presence of residual water.     

99mTc-labeled bombesin analog for breast cancer identification

Bombesin is a tetradecapeptide that binds specifically to gastrin releasing peptide receptors in humans. Several forms of cancer, including lung, prostate, breast, and colon express receptors for bombesin-like peptides. Radiolabeled bombesin analogs with a high affinity for these receptors might therefore be used for scintigraphic imaging of these tumor types. A truncated bombesin derivative (HYNIC-βAla-Bombesin_(7–14)) was radiolabeled with technetium-99m using EDDA and tricine as coligands. In vitro stability was evaluated in presence of plasma and excess of cysteine. The receptor-binding affinity assays was evaluated in MDA-MB-231 cancer cell line. In addition, in vivo biodistribution was performed in nude mice bearing breast tumor. In vitro assay showed a good affinity for the MDA-MB-231 cell line, showing 20.0 % of internalization at 4 h post-administration. ^99mTc-HYNIC-βAla-Bombesin_(7–14) biodistribution revealed a rapid clearance and a significant renal excretion. In addition, tumor uptake was higher than non-excretory organs, such as the spleen, the liver, and muscles. Tumor-to-muscle and tumor-to-blood ratios for ^99mTc-HYNIC-βAla-Bombesin_(7–14) showed high values at 4 h post-injection (5.34 and 4.55, respectively). Furthermore, blocked studies using cold bombesin peptide were performed, which demonstrated an important decrease in tumor uptake, indicating a tumor specificity for ^99mTc-HYNIC-βAla-Bombesin_(7–14). The ^99mTc-HYNIC-βAla-Bombesin_(7–14) displayed suitable radiochemical characteristics, and adequate affinity to breast tumor cells (MDA-MB-231). Therefore, this analog can be considered as a candidate for the identification of bombesin-positive tumors.     

Apoptosis mediated by caspase-3 and p53-dependent anticancer effects of 159Gd-DTPA-BMA complex

In this work the apoptosis mediated by caspase-3 and p53-dependent anticancer effects of ¹⁵⁹Gd-DTPA-BMA metal complex were evaluated against RT2 glioblastoma cells. The results showed that the mechanism of cell death involves apoptosis by caspase-3 activation. Furthermore, the involvement of p53 protein triggered by ¹⁵⁹Gd-DTPA-BMA in these cells was verified preliminarily. Considering these finding, the radioactive complex can be considered as potential therapeutic alternative agent against cancer.     

Evaluation of the optimal LNCaP prostate tumour developmental stage to be assessed by 99mTc-HYNIC-βAla-Bombesin(7–14) in an experimental model

The lymph node carcinoma of the prostate (LNCaP) cell line is widely used in prostate cancer diagnostic studies. However, the optimal developmental stage during which to assess LNCaP prostate tumours by in vivo molecular imaging has not been established. This study aimed to assess LNCaP prostate tumours by scintigraphic imaging using technetium-99m (^99mTc)-2-hydrazinonicotinamide (HYNIC)-beta-alanine (βAla)-Bombesin_(7–14) at different stages of tumour development and to compare each developmental stage using histopathological analysis. ^99mTc-HYNIC-βAla-Bombesin_(7–14) (7.4 MBq) was injected into LNCaP prostate tumour-bearing mice after 15, 20 or 25 days of tumour inoculation. Scintigraphic images were obtained 1 and 4 h following radiopeptide injection and tumour tissues were obtained for histopathological analysis. Tumours were not observed by scintigraphic imaging after 15 days of inoculation, but after 20 and 25 days of inoculation, tumours were visualised, with a tumour-to-muscle ratio of 2.14 at 4 h after the radiopeptide injection into mice with 25-day tumours. Histopathological analysis showed that the amount of collagen fibres in the stroma was inversely proportional to the stage of tumour development, whereas the intensity of vascular proliferation was directly proportional to the tumour stage; this explains radiopeptide localisation in LNCaP cells and improved visualisation of the 25-day tumours. In conclusion, the results showed that 25-day tumours presented the most appropriate features for radiopeptide accumulation in LNCaP cells, suggesting that they are in the best stage of tumour development to be assessed by scintigraphic imaging using ^99mTc-HYNIC-βAla-Bombesin_(7–14).     

Nearest-neighbour interaction from an Abelian symmetry and deviations from Hermiticity

We show that Nearest-Neighbour Interaction (NNI) textures for the quark mass matrices can be obtained through the introduction of an Abelian flavour symmetry. The minimal realisation requires a Z₄${\mathsf{Z}}_4$ symmetry in the context of a two Higgs doublet model. It is further shown that the NNI textures can be in agreement with all present experimental data on quark masses and mixings, provided one allows for deviations of Hermiticity in the quark mass matrices at the 20% level.     

The Use of Zidovudine Pharmacophore in Multi-Target-Directed Ligands for AIDS Therapy

The concept of polypharmacology embraces multiple drugs combined in a therapeutic regimen (drug combination or cocktail), fixed dose combinations (FDCs), and a single drug that binds to different targets (multi-target drug). A polypharmacology approach is widely applied in the treatment of acquired immunodeficiency syndrome (AIDS), providing life-saving therapies for millions of people living with HIV. Despite the success in viral load suppression and patient survival of combined antiretroviral therapy (cART), the development of new drugs has become imperative, owing to the emergence of resistant strains and poor adherence to cART. 3′-azido-2′,3′-dideoxythymidine, also known as azidothymidine or zidovudine (AZT), is a widely applied starting scaffold in the search for new compounds, due to its good antiretroviral activity. Through the medicinal chemistry tool of molecular hybridization, AZT has been included in the structure of several compounds allowing for the development of multi-target-directed ligands (MTDLs) as antiretrovirals. This review aims to systematically explore and critically discuss AZT-based compounds as potential MTDLs for the treatment of AIDS. The review findings allowed us to conclude that: (i) AZT hybrids are still worth exploring, as they may provide highly active compounds targeting different steps of the HIV-1 replication cycle; (ii) AZT is a good starting point for the preparation of co-drugs with enhanced cell permeability.