| 1. |
- Ciulla, M. M., et al.
(författare)
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Different effects of antihypertensive therapies based on losartan or atenolol on ultrasound and biochemical markers of myocardial fibrosis: results of a randomized trial
- 2004
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Ingår i: Circulation. - 1524-4539. ; 110:5, s. 552-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In hypertensive left ventricular hypertrophy (LVH), myocardial texture is altered by a disproportionate increase in fibrosis, but there is insufficient clinical evidence whether antihypertensive therapy or individual agents can induce regression of myocardial fibrosis. METHODS AND RESULTS: We compared the effects of an angiotensin II receptor antagonist with a beta-blocker on myocardial collagen volume (assessed by echoreflectivity and serum collagen markers) in 219 hypertensive patients with echocardiographically documented LVH. Patients were allocated randomly to receive losartan 50 to 100 mg/d (n=111) or atenolol 50 to 100 mg/d (n=99) with or without hydrochlorothiazide 12.5 to 25 mg/d for 36 weeks. Echoreflectivity analysis was conducted on ultrasound tracings of the midapex septum with specifically designed and validated software. A color histogram of reflecting echoes was obtained, and its spread (broadband [BB], previously shown to correlate directly with collagen volume fraction on endomyocardial biopsies) was used as the primary outcome measure. Mean color scale and serum markers of collagen synthesis (PIP, PIIIP) or degradation (CITP) were secondary outcome variables. Echoreflectivity analysis proved feasible in 106 patients (losartan 52, atenolol 54). Losartan reduced BB over 36 weeks (from 114.5 to 104.3 color levels, P<0.02), whereas atenolol treatment was associated with an increase in BB (from 109.0 to 113.6 color levels, P=NS), the difference between treatments being -12.8 color levels (95% CI -23.6 to -2.0, P=0.02). Secondary end points (mean color scale and collagen markers) also changed in the direction of decreased collagen in patients receiving losartan, but differences between groups were not statistically significant. CONCLUSIONS: In hypertensive patients with LVH, losartan decreases myocardial collagen content, whereas atenolol does not. The difference between the 2 treatments is statistically significant.
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| 2. |
- Cacciatore, I., et al.
(författare)
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Boron-based hybrids as novel scaffolds for the development of drugs with neuroprotective properties
- 2021
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Ingår i: RSC Medicinal Chemistry. - : Royal Society of Chemistry (RSC). - 2632-8682. ; 12:11, s. 1944-1949
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Tidskriftsartikel (refereegranskat)abstract
- Novel boron-based compounds (BBCs) were synthesized and evaluated as potential candidates for the development of novel drugs against Alzheimer's disease (AD). The neuroprotective profile of novel BBCs was evaluated using Aβ1-42-treated-SH-SY5Y cells while their antioxidant activity was evaluated by total antioxidant capacity (TAC) and total oxidative status (TOS) assays. Results showed that BLA (a novel boron-based hybrid containing an antioxidant portion) inhibited cell death induced by Aβ1-42-exposure in differentiated SH-SY5Y cells, resulting in an increase in cell viability by 25-33% (MTT assay) and by 63-71% (LDH assay) in a concentration range of 25-100 μM. Antioxidant assays demonstrated a good capability of BLA to counteract the oxidative status. Moreover, BLA possessed a significant ability to inhibit acetylcholinesterase (AChE) (22.96% at 50 μM), an enzyme whose enzymatic activity is increased in AD patients. In the present work, absorption and distribution properties of boron-based hybrids were predicted using Pre-ADMET software. In vitro preliminary results suggested that boron-based hybrids could be new structural scaffolds for the development of novel drugs for the management of AD.
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| 3. |
- Pagoni, A., et al.
(författare)
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Novel anti-Alzheimer phenol-lipoyl hybrids : Synthesis, physico-chemical characterization, and biological evaluation
- 2020
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier Masson SAS. - 0223-5234 .- 1768-3254. ; 186
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Tidskriftsartikel (refereegranskat)abstract
- To date, drugs that hit a single target are inadequate for the treatment of neurodegenerative diseases, such as Alzheimer's or Parkinson's diseases. The development of multitarget ligands, able to interact with the different pathways involved in the progession of these disorders, represents a great challenge for medicinal chemists. In this context, we report here the synthesis and biological evaluation of phenol-lipoyl hybrids (SV1-13), obtained via a linking strategy, to take advantage of the synergistic effect due to the antioxidant portions and anti-amyloid properties of the single constituents present in the hybrid molecule. Biological results showed that SV5 and SV10 possessed the best protective activity against Aβ1-42 induced neurotoxicity in differentiated SH-SY5Y cells. SV9 and SV10 showed remarkable antioxidant properties due to their ability to counteract the damage caused by H2O2 in SHSY-5Y-treated cells. Hovewer, SV5, showing moderate antioxidant and good neuroprotective activities, resulted the best candidate for further experiments since it also resulted stable both simulated and plasma fluids.
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| 4. |
- Özdemir, O., et al.
(författare)
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Anticancer effects of novel NSAIDs derivatives on cultured human glioblastoma cells
- 2020
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Ingår i: Zeitschrift für Naturforschung C - A Journal of Biosciences. - : Walter de Gruyter GmbH. - 0939-5075 .- 1865-7125.
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Tidskriftsartikel (refereegranskat)abstract
- Several epidemiologic, clinical and experimental reports indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) could have a potential as anticancer agents. The aim of this study was the evaluation of cytotoxic potential in human glioblastoma cells of novel synthesized NSAID derivatives, obtained by linking, through a spacer, α-lipoic acid (ALA) to anti-inflammatory drugs, such as naproxen (AL-3, 11 and 17), flurbiprofen (AL-6, 13 and 19) and ibuprofen (AL-9, 15 and 21). The effects on the level of gene expression were also determined using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. According to our results, NSAID derivatives exhibited concentration dependent cytotoxic effects on U87-MG cell line when compared with the control group. Moreover, treatment of the most active compounds (AL-3, AL-6 and AL-9) caused upregulation of tumor suppressor gene PTEN and downregulation of some oncogenes such as AKT1, RAF1 and EGFR. In conclusion, our results revealed that AL-3, AL-6 and AL-9 could be suitable candidates for further investigation to develop new pharmacological strategies for the prevention of cancer.
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