Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for several hematological diseases. Prospective and retrospective studies have associated myeloablative conditioning regimens with increased non-relapse mortality and less intense regimens with disease relapse, leading to similar overall survival rates. Analyze the experience with the different RIC schemes in patients transplanted for AML/MDS in our program.
View Article and Find Full Text PDFUnlabelled: Adiposity is a chronic disease that must be treated from childhood. Despite the transcendence of improving habits, few interventions report their contribution to decreasing adiposity.
Methods: This cohort enrolled children and teens of any gender, 8-18 years old, and with a body mass index (BMI) z-score of ≥1 into "Sacbe", a comprehensive program to identify which eating habits could reduce BMI z-score.
Adequate stem cell harvesting is required for autologous hematopoietic transplantation. In deficient mobilizer patients, the collection of stem cells can be challenging because of the impossibility of achieving satisfactory CD34 cell counts with GCSF + - chemotherapy. Plerixafor is a potent and expensive drug that promotes the release of stem cells from the medullary niche to the peripheral blood and allows satisfactory harvests.
View Article and Find Full Text PDFWe disclose a direct approach to the diastereoselective synthesis of phosphorus substituted -acylaziridines based on a one-pot ZnCl-catalyzed Joullié-Ugi three-component reaction of phosphorylated 2-azirines, carboxylic acids and isocyanides. Hence, this robust protocol offers rapid access to an array of -acylaziridines in moderate-to-good yields and up to 98:2 dr for substrates over a wide scope. The relevance of this synthetic methodology was achieved via a gram-scale reaction and the further derivatization of the nitrogen-containing three-membered heterocycle.
View Article and Find Full Text PDFBackground: The COVID-19 pandemic in 2020 profoundly impacted healthcare worldwide, and Peru was particularly affected, experiencing the highest COVID-19 case fatality rate globally.
Methods: We conducted a retrospective comparative study of patients presenting with aneurysmal subarachnoid hemorrhage (SAH) at a public Peruvian national referral center specializing in cerebrovascular diseases. Two study periods were considered, one during the first wave of the COVID-19 pandemic and a second identical period in 2019.
In the absence of a vaccine, there is a need to find new drugs for the treatment of neglected tropical diseases, such as leishmaniasis, that can overcome the many drawbacks of those currently used. These disadvantages include cost, the need to maintain a cold chain, the route of administration, the associated adverse effects and the generation of resistance. In this work we have evaluated the antileishmanial effect of 1,5- and 1,8-substituted fused naphthyridines through in vitro and ex vivo assays, using genetically modified axenic and intramacrophagic amastigotes.
View Article and Find Full Text PDFA cornerstone in drug discovery is the development of strategies to provide privileged small molecules with specific structural and stereochemical complexity, allowing access to new potential therapeutic entities. In this work, a new strategy based on the [4 + 2] Povarov reaction involving 1,3-diazadiene was developed. This approach is applied for a straightforward procedure in the preparation of chromeno[4,3-]pyrido[1,2-]pyrimidine derivatives, with accessible substrates, 2-aminopyridine and unsaturated aldehydes, and excellent atom economy to obtain four fused ring heterocycles, in a regio- and diastereoselective way.
View Article and Find Full Text PDFNitrogen heterocycles are part of the structure of natural products and agents with important biological activity, such as antiviral, antibiotic, and antitumor drugs. For this reason, heterocyclic compounds are one of today's most desirable synthetic targets and the Povarov reaction is a powerful synthetic tool for the construction of highly functionalized heterocyclic systems. This process involves an aromatic amine, a carbonyl compound, and an olefin or acetylene to give rise to the formation of a nitrogen-containing heterocycle.
View Article and Find Full Text PDFIntroduction: Person-centered care (PCC) includes life story, a form of reminiscence therapy that can be useful in the treatment of dementia. We compared the efficacy of using a digital or conventional life story book (LSB) on depressive symptoms, communication, cognition, and quality of life.
Material And Methods: Thirty one persons with dementia living in 2 PCC nursing homes were randomly assigned to receive reminiscence therapy based on the Neural Actions digital LSB (n=16) or a conventional LSB (n=15).
Introduction: The leukemic cells of patients with chronic lymphocytic leukemia (CLL) are often unique, expressing remarkably similar IGHV-IGHD-IGHJ gene rearrangements, "stereotyped BCRs". The B-cell receptors (BCRs) on CLL cells are also distinctive in often deriving from autoreactive B lymphocytes, leading to the assumption of a defect in immune tolerance.
Results: Using bulk and single-cell immunoglobulin heavy and light chain variable domain sequencing, we enumerated CLL stereotype-like IGHV-IGHD-IGHJ sequences (CLL-SLS) in B cells from cord blood (CB) and adult peripheral blood (PBMC) and bone marrow (BM of healthy donors.
New antibiotic agents were prepared using Povarov and Ugi multicomponent reactions upon the known drugs sulfadoxine and dapsone. The prepared derivatives, with increased lipophilicity, showed improved efficiency against Mycolata bacteria. Microbiological guidance for medicinal chemistry is a powerful tool to design new and effective antimicrobials.
View Article and Find Full Text PDFAn efficient general method for the synthesis of a wide family of α-aminophosphonate analogs of aspartic acid bearing tetrasubstituted carbons is reported through an aza-Reformatsky reaction of α-iminophosphonates, generated from α-aminophosphonates, in an umpolung process. In addition, the α-aminophosphonate substrates showed in vitro cytotoxicity, inhibiting the growth of carcinoma human tumor cell lines A549 (carcinomic human alveolar basal epithelial cell) and SKOV3 (human ovarian carcinoma). In view of the possibilities in the diversity of the substituents that offer the synthetic methodology, an extensive profile structure-activity is presented, measuring IC values up to 0.
View Article and Find Full Text PDFWe disclose the first accomplishment of the azo-Povarov reaction involving Sc(OTf)-catalyzed [4 + 2] annulations of -carbonyl aryldiazenes with cyclopentadiene in chloroform, in which -carbonyl aryldiazenes act as 4π-electron donors. Hence, this protocol offers a rapid access to an array of cinnoline derivatives in moderate to good yields for substrates over a wide scope. The synthetic potential of the protocol was achieved by the gram-scale reaction and further derivatization of the obtained polycyclic product.
View Article and Find Full Text PDFDigestive diseases are the fourth leading cause of outpatient care in Peruvian healthcare centers, with gastritis and peptic ulcers being the most common. This is a retrospective, cross-sectional, descriptive study of secondary analysis of medical record data to evaluate the prevalence of Helicobacter pylori in patients undergoing upper digestive endoscopy during 2019 at Clinica Delgado, Lima, Peru. An association between males (PRa 1.
View Article and Find Full Text PDFA study on the reactivity of 3-amino α,β-unsaturated γ-lactam derivatives obtained from a multicomponent reaction is presented. Key features of the substrates are the presence of an endocyclic α,β-unsaturated amide moiety and an enamine functionality. Following different synthetic protocols, the functionalization at three different positions of the lactam core is achieved.
View Article and Find Full Text PDFPharmaceuticals (Basel)
April 2022
We report efficient synthetic methodologies for the preparation of 3-amino and 3-hydroxy 3-pyrrolin-2-ones (unsaturated γ-lactams) through a multicomponent reaction of amines, aldehydes and acetylene or pyruvate derivatives. The densely substituted γ-lactam substrates show in vitro cytotoxicity, inhibiting the growth of the carcinoma human tumor cell lines RKO (human colon epithelial carcinoma), SKOV3 (human ovarian carcinoma) and A549 (carcinomic human alveolar basal epithelial cell). In view of the possibilities for the diversity of the substituents that offer a multicomponent, synthetic methodology, an extensive structure-activity profile is presented.
View Article and Find Full Text PDFClinical and molecular heterogeneity are hallmarks of chronic lymphocytic leukemia (CLL), a neoplasm characterized by accumulation of mature and clonal long-lived CD5 + B-lymphocytes. Mutational status of the IgHV gene of leukemic clones is a powerful prognostic tool in CLL, and it is well established that unmutated CLLs (U-CLLs) have worse evolution than mutated cases. Nevertheless, progression and treatment requirement of patients can evolve independently from the mutational status.
View Article and Find Full Text PDFExpert Opin Drug Discov
June 2022
Introduction: Cancer has been identified as one of the leading causes of death worldwide. The biological target of some anticancer agents is topoisomerase I, an enzyme involved in the relaxation of supercoiled DNA. The synthesis of new compounds with antiproliferative effect and behaving as topoisomerase I inhibitors has become an active field of research.
View Article and Find Full Text PDFThis work describes the first synthesis of diethyl 6,6a,7,11b-tetrahydro-5H-indeno[2,1-c]quinolinylphosphonates 5, diethyl 7H-indeno[2,1-c]quinolinylphosphonates 6 and diethyl 7-oxo-7H-indeno[2,1-c]quinolinylphosphonates 7, which were prepared in good to high overall yields. The synthetic route involves a multicomponent reaction of 2-phosphonateaniline, aldehydes and indene as olefin and allows the selective generation of three stereogenic centres in a short, efficient and reliable manner. The selective dehydrogenation of 1,2,3,4-tetrahydroindenoquinolines leads to the formation of corresponding indenoquinolines, and subsequent oxidation of methylene group of the indenoquinolines allows the access to indenoquinolinones.
View Article and Find Full Text PDFPrimary amoebic encephalitis (PAM) caused by the opportunistic pathogen is characterized as a rapid and lethal infection of the brain which ends in the death of the patient in more than 90% of the reported cases. This amoeba thrives in warm water bodies and causes infection after individuals perform risky activities such as splashing or diving, mostly in non-treated water bodies such as lakes and ponds. Moreover, the infection progresses very fast and no fully effective molecules have currently been found to treat PAM.
View Article and Find Full Text PDF: Eukaryotic topoisomerase 1 is a potential target of anti-parasitic and anti-cancer drugs. Parasites require topoisomerase 1 activity for survival and, consequently, compounds that inhibit topoisomerase 1 activity may be of interest. All effective topoisomerase 1 drugs with anti-cancer activity act by inhibiting the ligation reaction of the enzyme.
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