Synthesis and Identification of New N,N-Disubstituted Thiourea, and Thiazolidinone Scaffolds Based on Quinolone Moiety as Urease Inhibitor

Synthesis of thiazolidinone based on quinolone moiety was established starting from 4-hydroxyquinol-2-ones. The strategy started with the reaction of ethyl bromoacetate with 4-hydroxyquinoline to give the corresponding ethyl oxoquinolinyl acetates, which reacted with hydrazine hydrate to afford the hydrazide derivatives. Subsequently, hydrazides reacted with isothiocyanate derivatives to give the corresponding N,N-disubstituted thioureas. Finally, on subjecting the N,N-disubstituted thioureas with dialkyl acetylenedicarboxylates, cyclization occurred, and thiazolidinone derivatives were obtained in good yields. The two series based on quinolone moiety, one containing N,N-disubstituted thioureas and the other containing thiazolidinone functionalities, were screened for their in vitro urease inhibition properties using thiourea and acetohydroxamic acid as standard inhibitors. The inhibition values of the synthesized thioureas and thiazolidinones exhibited moderate to good inhibitory effects. The structure−activity relationship revealed that N-methyl quinolonyl moiety exhibited a superior effect, since it was proved to be the most potent inhibitor in the present series achieving (IC50 = 1.83 ± 0.79 µM). The previous compound exhibited relatively much greater activity, being approximately 12-fold more potent than thiourea and acetohydroxamic acid as references. Molecular docking analysis showed a good protein−ligand interaction profile against the urease target (PDBID: 4UBP), emphasizing the electronic and geometric effect of N,N-disubstituted thiourea. View Full-Tex

Regioselective synthesis of 5-aminopyrazoles from reactions of amidrazones with activated nitriles : NMR investigation and X-ray structural analysis

N-Arylbenzamidrazones and ethyl 2-cyano-3-ethoxybut-2-enoate reacted together in ethanol and catalyzed by triethylamine (Et3N) to give 5-amino-3-methyl-1-(aryl(phenylimino)methyl)-1H-pyrazole derivatives. Reaction of the target amidrazones with bis-(methylthio)methylidene)malononitrile in EtOH/Et3N/DMF mixture proceeded to give the corresponding 5-aminopyrazoles. The structure of the obtained products was proved by IR, mass, and NMR spectra and elemental analyses. Two-dimensional NMR spectroscopy and X-ray structural analyses were used to differentiate the assigned structures from other possible ring systems and regioisomers. The reaction mechanism is discussed.Peer reviewe

Regioselective formation of new 3-S-alkylated-1,2,4-triazole-quinolones

Regioselective synthesis of quinolone-1,2,4-triazoles was established starting from 4-hydroxyquinol-2-ones. The strategy started by the reaction of ethyl bromoacetate with 4-hydroxyquinoline to give the corresponding ethyl oxoquinolinyl acetates, which reacted with hydrazine hydrate to afford the hydrazide derivatives. Subsequently, hydrazides reacted with isothiocyanate derivatives to give the corresponding acyl thiosemicarbazides. Finally, subjecting the thiosemicarbazide derivatives with ethyl bromoacetate, the reaction underwent internal cyclization and alkylation processes. Alkylation occurred regioselectivity to the sulfur atom of the thione group and not to the amino group. Thus 3-S-1,2,4-triazole-quinolones were obtained in good yields. The structure of the obtained compounds was proved by different spectroscopic techniques together with elemental analysis and X-ray crystallography.Peer reviewe

Design, Synthesis and Biological Evaluation of Syn and Anti-like Double Warhead Quinolinones Bearing Dihydroxy Naphthalene Moiety as Epidermal Growth Factor Receptor Inhibitors with Potential Apoptotic Antiproliferative Action

Our investigation includes the synthesis of new naphthalene-bis-triazole-bis-quinolin-2(1H)-ones 4a–e and 7a–e via Cu-catalyzed [3 + 2] cycloadditions of 4-azidoquinolin-2(1H)-ones 3a–e with 1,5-/or 1,8-bis(prop-2-yn-1-yloxy)naphthalene (2) or (6). All structures of the obtained products have been confirmed with different spectroscopic analyses. Additionally, a mild and versatile method based on copper-catalyzed [3 + 2] cycloaddition (Meldal–Sharpless reaction) was developed to tether quinolinones to O-atoms of 1,5- or 1,8-dinaphthols. The triazolo linkers could be considered as anti and syn products, which are interesting precursors for functionalized epidermal growth factor receptor (EGFR) inhibitors with potential apoptotic antiproliferative action. The antiproliferative activities of the 4a–e and 7a–e were evaluated. Compounds 4a–e and 7a–e demonstrated strong antiproliferative activity against the four tested cancer cell lines, with mean GI50 ranging from 34 nM to 134 nM compared to the reference erlotinib, which had a GI50 of 33 nM. The most potent derivatives as antiproliferative agents, compounds 4a, 4b, and 7d, were investigated for their efficacy as EGFR inhibitors, with IC50 values ranging from 64 nM to 97 nM. Compounds 4a, 4b, and 7d demonstrated potent apoptotic effects via their effects on caspases 3, 8, 9, Cytochrome C, Bax, and Bcl2. Finally, docking studies show the relevance of the free amino group of the quinoline moiety for antiproliferative action via hydrogen bond formation with essential amino acids

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Microbial biopesticides affected age-stage life table of the tomato leaf miner, Tuta absoluta (Lepidoptera – Gelechiidae)

Abstract The tomato leaf miner, Tuta absoluta (Meyric), second instar larvae were exposed for 1 day to LC50 of Bacillus thuringiensis (Berliner) subsp. kurstaki or Beauveria bassiana (Balsamo) on treated tomato foliages. Treated larvae had the longest development period while non-treated larvae had the shortest development period. The highest survivorship (l x ) of adults was obtained by the non-treated larvae while the lowest survivorship was obtained by B. thuringiensis-treated larvae. The lowest age-specific fecundity (m x ) of females was obtained by individuals treated as second instar larvae with B. bassiana. The intrinsic rate of increase (r m ) reached its maximum with non-treated individuals while this value decreased to the minimum values with biopesticide-treated individuals. Therefore, development, survival, and reproduction of treated individuals were lower than those of non-treated individuals. The reproduction period and adult longevity were the shortest considering biopesticide-treated individuals. The highest and lowest net reproductive rates (R 0) were recorded for non-treated and treated individuals, respectively. The mean generation time was increased with biopesticide-treated individuals

Comparing the salinity tolerance of twenty different wheat genotypes on the basis of their physiological and biochemical parameters under NaCl stress.

The climate has drastically changed over the past two decades. Rising temperatures and climate change may lead to increased evapotranspiration, specifically soil evaporation, causing water to evaporate and salt to accumulate in the soil, resulting in increased soil salinity. As a result, there is a need to evaluate methods for predicting and monitoring the effects of salinity on crop growth and production through rapid screening. Our study was conducted on 20 wheat genotypes, 10 sensitive and 10 tolerant, exposed to two salinity levels (90 and 120 mM NaCl) with the control under greenhouse conditions. Our results revealed significant differences in the genotypes' response to salinity. Salt stress decreased chlorophyll index in sensitive genotypes but increased chlorophyll a and carotenoids in tolerant genotypes at 90 mM. Salt stress also increased protein, proline, lipoxygenase, and reactive thiobarbituric acid levels in all wheat genotypes. The study suggests that plant photosynthetic efficiency is a reliable, non-destructive biomarker for determining the salt tolerance of wheat genotypes, while other biochemical traits are destructive and time-consuming and therefore not suitable for rapid screening

Comparative physiological and biochemical mechanisms in diploid, triploid, and tetraploid watermelon (Citrullus lanatus L.) grafted by branches

Abstract Seed production for polyploid watermelons is costly, complex, and labor-intensive. Tetraploid and triploid plants produce fewer seeds/fruit, and triploid embryos have a harder seed coat and are generally weaker than diploid seeds. In this study, we propagated tetraploid and triploid watermelons by grafting cuttings onto gourd rootstock (C. maxima × C. mochata). We used three different scions: the apical meristem (AM), one-node (1N), and two-node (2N) branches of diploid, triploid, and tetraploid watermelon plants. We then evaluated the effects of grafting on plant survival, some biochemical traits, oxidants, antioxidants, and hormone levels at different time points. We found significant differences between the polyploid watermelons when the 1N was used as a scion. Tetraploid watermelons had the highest survival rates and the highest levels of hormones, carbohydrates, and antioxidant activity compared to diploid watermelons, which may explain the high compatibility of tetraploid watermelons and the deterioration of the graft zone in diploid watermelons. Our results show that hormone production and enzyme activity with high carbohydrate content, particularly in the 2–3 days after transplantation, contribute to a high survival rate. Sugar application resulted in increased carbohydrate accumulation in the grafted combination. This study also presents an alternative and cost-effective approach to producing more tetraploid and triploid watermelon plants for breeding and seed production by using branches as sprouts