Crystal structure, spectroscopy, DFT, and thermal studies of 3-cyano-2(1H)-pyridones as potential anticancer agents.

A series of 3-cyano-2(1H)-pyridones 4a-c were efficiently synthesized using an expeditious microwave-assisted multicomponent approach. Single-crystal XRD analysis revealed the presence of six independent molecules in the asymmetric unit cell for all compounds, with the crystal packing stabilized by a network of cyclic dimers formed by N-H⋯O[double bond, length as m-dash]C and C-H⋯O[double bond, length as m-dash]C intermolecular interactions. Additional supramolecular interactions, including C-H⋯π, C-N⋯π, and π⋯π, and C-H⋯X (for halogenated derivatives, i.e., 4b and 4c), appear crucial for crystal stabilization. Density Functional Theory (DFT) calculations were employed to understand the electronic structures and potential binding affinities. Comprehensive spectroscopic characterization by FT-IR, UV-Vis, NMR, and HMRS techniques confirmed the structures of all synthesized compounds. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were employed to evaluate the thermal stability of these compounds. The in vitro anticancer activity was evaluated against a panel of 60 human cancer cell lines, demonstrating promising activity against non-small-cell lung and breast cancer cell lines. Notably, compounds 4a and 4c exhibited the highest anticancer activity against the HOP-92 and MCF7 cell lines, with growth inhibition percentages (GI%) of 54.35 and 40.25, respectively.

Exploring uterine contractility frequency in infertile population: A comparative study among different control groups with and without a C-section defect.

OBJECTIVE: Women undergoing IVF who have had a previous c-section (CS) have a lower live birth rate than those with a previous vaginal delivery. However, the precise underlying mechanisms need clarification. Does a previous CS affect the pattern of uterine contractility?. METHODS: Prospective evaluation in patients undergoing frozen blastocyst embryo transfer in medicated endometrial preparation cycles. Twenty patients were included in groups: A/nulliparous. B/previous vaginal delivery. C/ previous CS without a niche, whereas fifteen patients were recruited in group D (CS and a niche). Patients employed estradiol compounds and 800 mg vaginal progesterone. A 3D-scan was performed the transfer-day where uterine contractility/minute was recorded. RESULTS: Baseline characteristics (age, BMI, smoking, endometrial thickness) were similar. Mean frequency of uterine contractions/minute was similar between groups (1.15, 1.01, 0.92, and 1.21 for groups A, B, C, and D, respectively). There was a slight increase in the number of contractions in patients with a sonographic niche versus controls, not reaching statistical significance (p=0.48). No differences were observed when comparing patients with a previous C-section (regardless of the presence of a niche) to those without a C-section, either nulliparous (p=0.78) or with a previous vaginal delivery (p=0.80). The frequency of uterine contractions was similar between patients who achieved a clinical pregnancy and those who did not (1.19 vs. 1.02 UC/min, p=0.219, respectively). CONCLUSIONS: Our study found no significant difference in the frequency of uterine contractility between patients with or without a previous C-section or sonographic diagnosed niche. Further investigation is necessary to understand the physiological mechanisms affecting implantation in patients with isthmocele.

Microwave-assisted synthesis and functionalization of 2-arylimidazo[1,2-a]pyrimidin-5(8H)-ones.

Despite the limited applications and scarcity of commercial examples of imidazo[1,2-a]pyrimidines, their exceptional properties hold great potential, representing a significant challenge in discovering more critical applications. Herein, we present a microwave-assisted approach for preparing 2-arylimidazo[1,2-a]pyrimidin-5(8H)-ones and their alkylation and bromination products using easily accessible and inexpensive reagents, thus offering a promising avenue for further search. Notably, the photophysical properties of an N-alkyl derivative were investigated, and the results highlight the high potential of these compounds as modular fluorophores. All the products were obtained with high yields using highly efficient protocols, and the regioselectivity of the reactions was determined on the basis of NMR measurements and X-ray diffraction analysis.

Continuous ovarian stimulation: a proof-of-concept study exploring the uninterrupted use of corifollitropin α in DuoStim cycles for enhanced efficiency and patient convenience (Alicante protocol).

Objective: To explore the use of weekly continuous dosing of corifollitropin α in DuoStim cycles. Design: Pilot-matched case-control study. Setting: Private fertility center. Patients: Cases were defined as DuoStim cycles performed from November 2022 to May 2023 receiving weekly continuous dosing of corifollitropin α (n = 15). Controls were chosen from a database comprising DuoStim cycles conducted at our institution during the years 2021/2022. Matching was done on a 1-to-1 basis, based on antimüllerian hormone values (±0.4 pmol/L) and age (n = 15). Interventions: Injections of corifollitropin α once every 8 days, along with uninterrupted oral administration of micronized progesterone 200 mg/d (for luteinizing hormone surge prevention) throughout the follicular and luteal phases for ovarian stimulation. Oocyte retrieval. Main outcome measures: Total number of cumulus-oocyte complexes and metaphase II oocytes obtained in follicular + luteal phase stimulation. Secondary outcomes evaluated fertilization rates, number of blastocysts, days of stimulation, number of injectables required, and gonadotropin cost. Results: The study group achieved similar total oocyte and MII yield vs. daily follicle-stimulating hormone protocol (13.3 ± 6.9 vs. 11.8 ± 6.1 and 10.4 ± 6.3 vs. 9.2 ± 4.6, respectively). All secondary outcomes showed no significant differences. The study group experienced a significant reduction of injections to complete a DuoStim cycle (4.5 ± 1.4 vs. 35.2 ± 12.2; mean deviation -30.7; 95% confidence interval, -37.5- to -23.9)]. Conclusions: Corifollitropin α on a weekly basis throughout a DuoStim cycle yields an equivalent number of oocytes as standard daily follicle-stimulating hormone administration while drastically reducing the number of required injections. Trial registration number: NCT05815719. EudraCT: 2022-003177-32.

Cs2CO3-Promoted Alkylation of 3-Cyano-2(1H)-Pyridones: Anticancer Evaluation and Molecular Docking.

Herein, a Cs2CO3-promoted N-alkylation of 3-cyano-2(1H)-pyridones containing alkyl groups with diverse alkyl halides to synthesize N-alkyl-2-pyridones over O-alkylpyridines is reported. The use of alkyl dihalides resulted in complex mixtures of N- and O-alkylated products. The primary factor influencing regioselectivity in these reactions is the electronic effects of substituents on the 2(1H)-pyridone ring, as evidenced by the preferential formation of O-alkylpyridines upon the introduction of aryl groups. Remarkably, we efficiently employed CuAAC and Ti(Oi-Pr)4-catalyzed amidation reactions to functionalize N-alkyl-2-pyridones containing propargyl and ester groups, leading to the synthesis of 1,2,3-triazoles and amides, respectively. Moreover, O-alkylpyridines 10 b and 10 d displayed remarkable selectivity toward the A-498 renal cancer cell line with growth inhibition percentages (%GI) of 54.75 and 67.64, respectively. The binding modes of compounds 10 b and 10 d to the PIM-1 kinase enzyme were determined through molecular docking studies.

The impact of (very) young donor age on euploid rates: An analysis of 1831 trophectoderm biopsies evaluated with 24-chromosome NGS screening in oocyte donation cycles.

RESEARCH QUESTION: Conflicting data exists regarding whether a younger age of donors has a negative influence on the outcomes of oocyte donation cycles. Is there any correlation between a younger age of donors and the rate of embryonic aneuploidy in oocyte donation cycles? DESIGN: Retrospective study including 515 oocyte donation cycles carried out between February 2017 and November 2022. Comprehensive chromosomal screening was performed on 1831 blastocysts. 1793 had a result which were categorised into groups based on the age of the donor: 18-22 (n = 415), 23-25 (n = 600), 26-30 (n = 488), and 31-35 years (n = 290). The analysis aimed to determine the percentage of biopsy samples that were euploid and the number that were aneuploid, relative to the age group of the oocyte donor. Additionally, linear regression was employed to examine the relationship between age and the proportion of aneuploid embryos, while controlling for relevant variables. RESULTS: Aneuploidy increased predictably with donor age: 18-22 years: 27.5 %; 23-25 years: 31.2 %; 26-30 years: 31.8 %; and 31-35 years: 38.6 %. In the donor group aged 31-35 years, a higher percentage of aneuploid embryos was observed compared to younger donors in univariate analysis (OR: 1.66, 95 % CI: 1.21-2.29, p = 0.002) and multivariate logistic analysis (OR: 2.65, 95 % CI: 1.67-4.23, p < 0.001). The rates of embryonic mosaicism revealed no significant differences. CONCLUSION: The lowest risk of embryonic aneuploidy was found among donors aged <22 years. Conversely, an elevated prevalence was evident within the donor group aged 31-35 years, in contrast to the younger cohorts. The incidence of mosaic embryos remained consistent across all age groups.

Random-start ovarian stimulation in an oocyte donation programme: a large, single-centre, experience.

RESEARCH QUESTION: Do live birth rates differ between recipients matched with donors using conventional ovarian stimulation compared with those using random-start protocols? DESIGN: Retrospective analysis of 891 ovarian stimulations in egg donors (January-December 2018) and clinical outcomes in matched recipients (n = 935). Donors commenced ovarian stimulation on day 1-3 of the menstrual cycle (n = 223) or in the mid/late-follicular (n = 388) or luteal phase (n = 280) under a conventional antagonist protocol. Live birth rate of matched recipients was the main outcome. RESULTS: Duration of stimulation and total gonadotrophin dose were comparable between conventional versus random-start groups. The number of collected eggs were similar (17.6 ± 8.8 versus 17.2 ± 8.5, P = 0.6, respectively). Sub-group analysis showed that stimulation length (10.2 ± 1.8 versus 9.8 ± 1.7 versus 10.4 ± 1.7, P < 0.001) and gonadotrophin consumption (2041.5 ± 645.3 versus 2003.2 ± 647.3 versus 2158.2 ± 685.7 IU, P = 0.01) differed significantly between the conventional, mid/late follicular and luteal phase groups, respectively. In matched recipients receiving fresh oocytes and undergoing fresh embryo transfer, the biochemical pregnancy (63.8% and 63.3%; P = 0.9), clinical pregnancy (54.6% and 56.1%; P = 0.8) and live birth rates (47.7% and 46.6%; P = 0.7) per embryo-transfer were similar between conventional versus random groups. Similar results were obtained in recipients receiving vitrified eggs. Euploidy rate was also comparable. CONCLUSIONS: No notable variations were found in clinical outcomes using oocytes obtained from random-start protocols and those proceeding from conventional ovarian stimulation in oocyte donation treatments. Luteal-phase stimulation seems to require longer stimulation and higher FSH consumption. Random-start stimulation strategy does not impair the potential of the oocyte yield or clinical outcomes in oocyte donation cycles.

Crystallographic, spectroscopic and thermal studies of 1-(4-bromophenyl)-5-(2,5-dimethyl-1H-pyrrol-1-yl)-3-methyl-1H-pyrazole.

The new title pyrrole-pyrazole derivative, C16H16BrN3, was synthesized through a citric acid-catalyzed Paal-Knorr reaction between acetonylacetone and 1-(4-bromophenyl)-3-methyl-1H-pyrazol-5-amine under mild reaction conditions. This synthetic protocol is noteworthy for its utilization of stoichiometric amounts of the reactants, an ecofriendly solvent and a cost-effective, non-toxic and biodegradable organocatalyst. A comprehensive understanding of the molecular structure was gained through spectroscopic, thermal and X-ray crystallographic analyses. The crystal structure is characterized by weak interactions, where only C-H...π connections contribute to the hydrogen-bond contacts. The supramolecular assembly is controlled by dispersion forces. However, the energy frameworks demonstrate that these forces act in three dimensions, providing enough stability, as observed in TGA-DSC (thermogravimetric analysis-differential scanning calorimetry) studies.

Biochar-MgO from Soursop Seeds in the Production of Biofuel Additive Intermediates.

The conversion of residual biomass from fruit seeds into biochar can be achieved using MgCl2 as an activating agent and calcining at 700 °C. The resulting MgO-biochars were employed in the aldol condensation reaction between furfural and acetone. This reaction is essential as the first step in the obtention of biofuels derived from biomass. The biochars were characterized through various physicochemical techniques, revealing that the presence of MgO nanoparticles deposited on the carbon surface modifies the structural and acidic-basic properties of the carbonaceous materials with a graphitic structure. The biochar with a surface content of MgO of 0.34 % w/w enables the achievement of 100 % of selectivity towards 4-(2-furanyl)-3-buten-2-one (I) with quantitative conversions under optimized conditions. This property highlights the potential of using this type of biochar, commonly used for CO2 capture, as a versatile acidic-basic catalyst, thereby introducing a novel approach to sustainable chemistry.

Synthesis and Biological Studies of Benzo[b]furan Derivatives: A Review from 2011 to 2022.

The importance of the benzo[b]furan motif becomes evident in the remarkable results of numerous biological investigations, establishing its potential as a robust therapeutic option. This review presents an overview of the synthesis of and exhaustive biological studies conducted on benzo[b]furan derivatives from 2011 to 2022, accentuating their exceptional promise as anticancer, antibacterial, and antifungal agents. Initially, the discussion focuses on chemical synthesis, molecular docking simulations, and both in vitro and in vivo studies. Additionally, we provide an analysis of the intricate interplay between structure and activity, thereby facilitating comparisons and profoundly emphasizing the applications of the benzo[b]furan motif within the realms of drug discovery and medicinal chemistry.

Progesterone levels on the day of embryo transfer using a single pessary of 400mg of vaginal progesterone vs. 200mg x2 pessaries in hormonal replacement cycles.

OBJECTIVE: Does the use of 400mg pessaries of micronized progesterone provide comparable results as pessaries of 200mg x2, in terms of progesterone levels in hormonal replacement cycles for embryo transfer?. METHODS: Retrospective cohort study based on 299 embryo transfer treatments under artificial endometrial preparation carried out at Instituto Bernabeu. 131 patients received 1 pessary of 400 mg b.i.d. (group A) and 168 received 2 pessaries of 200 mg b.i.d. (group B). RESULTS: Mean serum progesterone levels were similar between groups (A: 13.64±4.47ng/mL vs. B: 13.88±7.17ng/mL). There were no differences in suboptimal progesterone levels between groups (A: 11.5% vs. B: 16.8%). In terms of patients receiving additional progesterone supplementation, there were no differences between groups (A: 26% vs. B: 35.3%.). No differences between groups were observed in clinical outcomes: pregnancy rate (PR) (A: 55% vs. B: 54.8%), biochemical pregnancy loss rate (BPLR) (A: 13.4% vs. B: 17.6%), miscarriage rate (MR) (A: 17.9% vs. B: 19.8%) and ongoing pregnancy rate (OPR) (A: 36.5% vs. B: 34.1%). CONCLUSIONS: One progesterone pessary of 400mg (Cyclogest®) twice daily appears to be non-inferior to the use of two-200mg pessaries twice daily in terms of progesterone levels in HRT cycles.

Influence of the starting day of luteal phase stimulation on double stimulation cycles.

Background: Double ovarian stimulation is one of the most used strategies in poor-prognosis patients. There is a high heterogeneity between the studies regarding the execution of this stimulation protocol. The aim of this study was to investigate whether the day on which luteal phase stimulation begins after the first oocyte retrieval affects ovarian response in DuoStim cycles. Methods: This observational and retrospective study included 541 DuoStim cycles between January 2018 and December 2021 in a private fertility clinic. Patients were assigned to 4 groups according to the timing of the onset of luteal phase stimulation after oocyte retrieval (0-2nd day, 3rd day, 4th day and 5th-6th day). The primary outcome was the number of oocytes retrieved in the luteal phase in each group. Results: No differences were found between groups in the number of oocytes collected (5.12 ± 3.56 vs. 5.39 ± 3.74 vs. 5.61 ± 3.94 vs. 5.89 ± 3.92; p=0,6), MII or number of follicles. An increase in the duration of stimulation was found when stimulation started on the 4th day (10.42 ± 2.31 vs. 10.68 ± 2.37 vs. 11.27 ± 2.40 vs. 10.65 ± 2.37 days, p=0,033). A lower number of fertilized oocytes was observed when stimulation began before the fourth day (3.36 ± 2.80 vs. 3.95 ± 2.53 vs. 4.03 ± 2.73 vs. 4.48 ± 3.11; p=0,036). The number of blastocysts was higher when the stimulation started 5-6 days after retrieval (1.82 ± 1.74 vs. 2.13 ± 1.61 vs. 2.33 ± 2.06 vs. 2.91 ± 2.39; p= 0,030). Discussion: The number of oocytes retrieved does not differ depending on the day that stimulation begins. However, oocytes competence in terms of fertilized oocytes and blastulation, appears to be lower when the second stimulation starts before the fourth day after oocyte retrieval.

Colaboración y cooperación con las entidades municipales y otros sectores económicos y sociales / Collaboration and cooperation with municipal entities and other economic and social sectors

El trabajo conjunto y estrecho con las entidades municipales y los sectores económicos ysociales ha sido una de las áreas de desempeño más importes del Departamento de Saluddurante la pandemia de COVID-19. La comunicación directa y fluida, la transmisión deinformación fidedigna, y la puesta en marcha de procesos bilaterales y participados han sidoelementos de gran valor en un contexto dinámico, volátil y sin precedentes. Han permitidotransmitir tranquilidad en momentos de tensionamiento, hacer partícipes activos a los agentesen el desarrollo de las medidas, o facilitar el entendimiento de las diferentes normativas, loque ha favorecido su aplicación práctica.(AU)

Exploring self-detection of the endogenous LH surge using a urine test as a tool to predict a suboptimal response to gonadotropin-releasing hormone agonist trigger during in vitro fertilization cycles.

OBJECTIVE: Is self-detection of the endogenous LH surge using a urine testing a reliable method to confirm a successful gonadotropin-releasing hormone agonist (GnRHa) trigger in IVF cycles? METHODS: Prospective observational study including a total of 103 oocyte donation cycles between November 2019 and January 2020. Urine LH testing (Akralab SL, Spain, cut-of value 30 mIU/mL) was performed at home in samples from the first micturition in the morning after the GnRHa trigger and a picture of the result was sent to the nurse coordinator; this information was concealed and only disclosed after oocyte aspiration. RESULTS: From the total group, two cycles were excluded. A total of 101 oocyte donors performed the LH urine testing, all proceeded to oocyte aspiration and were included in final analysis. A total of 85 (84.2%) had a positive LH test and an uneventful oocyte retrieval with good retrieval rates (false positive rate: 0%). A total of 16 had a negative LH test (15.8%) and had a good oocyte retrieval rates (false negative rate: 15.8%). There were no cases of empty follicle syndrome. CONCLUSIONS: Due to a high false negative rate, self-testing of endogenous LH release using a LH urine test when performed approximately 12-hours after triggering does not seem to be a reliable method to predict a suboptimal response to gonadotropin-releasing hormone.

Does mRNA COVID-19 vaccination in oocyte donors impact ovarian stimulation parameters or IVF outcomes for recipients?

RESEARCH QUESTION: What is the effect of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in young oocyte donors in terms of ovarian response to stimulation, fertilization rate, embryo development and clinical outcomes in recipients? DESIGN: This retrospective, multicentre cohort study evaluated 115 oocyte donors who had undergone at least two ovarian stimulation protocols (before and after complete SARS-CoV-2 vaccination) between November 2021 and February 2022. Comparisons were made of the primary outcomes of days of stimulation, total dose of gonadotrophins and laboratory performance in ovarian stimulation in oocyte donors before and after vaccination. A total of 136 cycles in matched recipients were analysed as secondary outcomes and, from those, 110 women received a fresh single-embryo transfer, with analysis of biochemical ß-human chorionic gonadotrophin concentrations and rates of clinical pregnancy with heartbeat. RESULTS: Longer stimulation was required in the post-vaccination than pre-vaccination group (10.31 ± 1.5 versus 9.51 ± 1.5 days; P < 0.001) along with higher gonadotrophin consumption (2453.5 ± 740 versus 2235.5 ± 615 IU; P < 0.001) with a similar starting dose of gonadotrophins in both groups. More oocytes were retrieved in the post-vaccination group (16.62 ± 7.1 versus 15.38 ± 7.0; P = 0.02). However, the number of metaphase II (MII) oocytes was similar between groups (pre-vaccination 12.61 ± 5.9 versus post-vaccination 13.01 ± 6.6; P = 0.39) and the ratio of MII/retrieved oocytes favoured the pre-vaccination group (0.83 ± 0.1 versus 0.77 ± 0.2 post-vaccination; P = 0.019). In recipients with a similar number of provided oocytes, the fertilization rate, total number of obtained blastocysts, number of top-quality blastocysts, and rates of biochemical pregnancy and clinical pregnancy with heartbeat were not significantly different between groups. CONCLUSIONS: This study shows no adverse influence of mRNA SARS-CoV-2 vaccination on ovarian response in a young population.

Conventional follicular-phase ovarian stimulation vs. luteal-phase stimulation in suboptimal responders: a randomized controlled trial.

Objective: To compare the oocyte yield between follicular-phase stimulation (FPS) and luteal-phase stimulation (LPS) in suboptimal responders. Design: Prospective, randomized, crossover clinical trial. Patients: Forty-one patients with infertility according to the POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) criteria (1b/2b). Interventions: Crossover study on 2 assigned ovarian stimulations that started randomly in the follicular or luteal phase. The in vitro fertilization cycles were not consecutive but separated in time (45 days to 6 months). The random crossover design ensured that all subjects received the first treatment by chance. Main Outcome Measures: The primary objective was the number of cumulus-oocyte complexes retrieved in each cycle. Secondary objectives were number of metaphase II and fertilized oocytes, additional doses of recombinant follicle-stimulating hormone, and the duration of ovarian stimulation (days). Results: The mean number of cumulus-oocyte complexes retrieved was similar between the FPS and LPS groups (7.5 ± 4.6 vs. 7.0 ± 4.1; 95% confidence interval [CI] for the mean, 5.8-8.7 vs. 5.6-8.3, respectively; the difference between means, -0.5; 95% CI, -1.8 to +1.5). Similarly, the mean number of metaphase II oocytes retrieved was not different between the FPS and LPS groups (5.4 ± 3.6 vs. 5.2 ± 2.8; 95% CI for the mean, 4.2-6.5 vs. 4.3-6.1, respectively; the difference between means, -0.2; 95% CI, -1.2 to +1.1). Moreover, the secondary objectives were similar between FPS and LPS groups. Conclusions: In this study, the oocyte yield in LPS did not increase in suboptimal responders compared with that in FPS when the onset of LPS was separated in time from FPS. Clinical Trial Registration Number: NCT039393990 https://beta.clinicaltrials.gov/study/NCT03939390.

Bioactive 2-pyridone-containing heterocycle syntheses using multicomponent reactions.

2-Pyridone-containing heterocycles are considered privileged scaffolds in drug discovery due to their behavior as hydrogen bond donors and/or acceptors and nonpeptidic mimics, and remarkable physicochemical properties such as metabolic stability, solubility in water, and lipophilicity. This review provides a comprehensive overview of multicomponent reactions (MCRs) for the synthesis of 2-pyridone-containing heterocycles. In particular, it covers the articles published from 1999 to date related to anticancer, antibacterial, antifungal, anti-inflammatory, α-glucosidase inhibitor, and cardiotonic activities of 2-pyridone-containing heterocycles obtained exclusively by an MCR. The discussion focuses on bioactivity data, synthetic approaches, plausible reaction mechanisms, and molecular docking simulations to facilitate comparison and underscore the applications of the 2-pyridone motif in drug discovery and medicinal chemistry. We also present our conclusions and outlook for the future.

Effects of polycyclic aromatic hydrocarbons on gestational hormone production in a placental cell line: Application of passive dosing to in vitro tests.

Air pollution includes polycyclic aromatic hydrocarbons (PAHs), which have been correlated to endocrine disruptor pathways during early pregnancy. PAHs have been found in the placenta and cord blood, which may affect the hormones involved in placental development. We studied the effects of some airborne PAHs on beta human chorionic gonadotropin (ß-hCG) and progesterone production by using a syncytial BeWo cell line as a placental model. PAH congeners were spiked in silicon rubber membrane (SRMs) and were then introduced into the cell medium by the passive dosing method to reach a freely dissolved concentration for BeWo cell exposure. Ultrahigh-performance liquid chromatography coupled with a diode array detector was used to analyze the PAHs, and electrochemiluminescence was used to test the hormone levels. Our results showed that passive dosing can deliver low levels of PAH congeners in the cell medium, which allowed us to calculate the individual release constants at equilibrium and to estimate their effects. Benzo[a]pyrene was released quickly from the SRMs to the cell medium, which can be attributed to its lipophilic properties. The PAHs were shown to decrease the ß-hCG level in the short term and progesterone level in the long term, so they may serve as a pathway for endocrine disorder in trophoblastic cells. This approximation may explain observations of impaired endometrium receptivity and placental dysfunction, which enhance adverse pregnancy outcomes such as embryonic mortality and intrauterine growth restriction.

Recent Applications of the Multicomponent Synthesis for Bioactive Pyrazole Derivatives.

Pyrazole and its derivatives are considered a privileged N-heterocycle with immense therapeutic potential. Over the last few decades, the pot, atom, and step economy (PASE) synthesis of pyrazole derivatives by multicomponent reactions (MCRs) has gained increasing popularity in pharmaceutical and medicinal chemistry. The present review summarizes the recent developments of multicomponent reactions for the synthesis of biologically active molecules containing the pyrazole moiety. Particularly, it covers the articles published from 2015 to date related to antibacterial, anticancer, antifungal, antioxidant, α-glucosidase and α-amylase inhibitory, anti-inflammatory, antimycobacterial, antimalarial, and miscellaneous activities of pyrazole derivatives obtained exclusively via an MCR. The reported analytical and activity data, plausible synthetic mechanisms, and molecular docking simulations are organized in concise tables, schemes, and figures to facilitate comparison and underscore the key points of this review. We hope that this review will be helpful in the quest for developing more biologically active molecules and marketed drugs containing the pyrazole moiety.

Improving the Annotation of the Venom Gland Transcriptome of Pamphobeteus verdolaga, Prospecting Novel Bioactive Peptides.

Spider venoms constitute a trove of novel peptides with biotechnological interest. Paucity of next-generation-sequencing (NGS) data generation has led to a description of less than 1% of these peptides. Increasing evidence supports the underestimation of the assembled genes a single transcriptome assembler can predict. Here, the transcriptome of the venom gland of the spider Pamphobeteus verdolaga was re-assembled, using three free access algorithms, Trinity, SOAPdenovo-Trans, and SPAdes, to obtain a more complete annotation. Assembler's performance was evaluated by contig number, N50, read representation on the assembly, and BUSCO's terms retrieval against the arthropod dataset. Out of all the assembled sequences with all software, 39.26% were common between the three assemblers, and 27.88% were uniquely assembled by Trinity, while 27.65% were uniquely assembled by SPAdes. The non-redundant merging of all three assemblies' output permitted the annotation of 9232 sequences, which was 23% more when compared to each software and 28% more when compared to the previous P. verdolaga annotation; moreover, the description of 65 novel theraphotoxins was possible. In the generation of data for non-model organisms, as well as in the search for novel peptides with biotechnological interest, it is highly recommended to employ at least two different transcriptome assemblers.