Triethyl ammonium sulphate catalyst one pot, Solvent free synthesis of novel Coumarin derivatives as antimicrobial agents

The 20th International Electronic Conference on Synthetic Organic Chemistry session Ionic LiquidsThe work reports synthesis of 15 novel 3-((dicyclohexylamino)(substituted phenyl/heteryl)methyl)-4-hydroxy-2H-chromen-2-one derivatives 4 (a-o) as potential antimicrobial agents in solvent-free condition using Triethyl ammonium sulphate [Et3NH][HSO4] as an efficient, eco-friendly and reusable catalyst. Compared to other methods, this new method consistently has advantages, including excellent yields, a short reaction time, mild reaction conditions and catalyst reusability. The heterocyclic compound Coumarin, is associated with diverse biological activities of immense importance. Due to the presence of coumarin moiety in various pharmaceutically active compounds, we planned the green synthesis of a series of 15 novel compounds containing coumarin moiety coupled with dicyclohexyl rings by an eco-friendly ionic-liquid mediated protocol at room temperature by stirring. The structures of the synthesized compounds were confirmed by spectral characterization such as IR, 1H NMR, 13CNMR and Mass spectral studies. All the synthesized compounds 4 (a-o) were evaluated for anti-fungal and antibacterial activities and have exhibited promising antimicrobial activit

Microwave-assisted Facile Synthesis And Anticancer Evaluation Of N-((5-(substituted Methylene Amino)- 1,3,4-thiadiazol-2-yl)methyl) Benzamide Derivatives

The 20th International Electronic Conference on Synthetic Organic Chemistry session General Organic SynthesisMicrowave induced synthesis has various advantages over conventional synthesis, such as highly accelerated reaction rate , reasonable better yields, simple open systems, no solvent or very less amount of solvents required, eco friendly method, clean heating system and control on reaction parameters .In the present work novel Schiff’s bases containing thiadiazole scaffold and benzamide group, through appropriate pharmacophore were designed and synthesized , because of the important biological properties associated with these three moieties/groups. The coupling of these important moieties was achieved under microwave irradiation. A facile, solvent-free synthesis of a series of N-((5-(substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl)benzamide was carried out under microwave-irradiation. Solvent free synthesis of novel Schiff bases was achieved by cyclo-addition of various aromatic aldehydes (0.01 mol) and N-((5-amino-1,3,4-thiadiazol-2-yl)methyl)benzamide(0.01 mol)in presence of catalytic amount of glacial acetic acid under microwave irradiation. The same compounds were also synthesized using conventional approach. The conventional method required 15-18 hrs, while microwave irradiation method required only 15-20 minutes and gave better yields. Total 12 final compounds were synthesized as per the scheme reported. Structures of synthesized compounds were confirmed by IR, NMR, and Mass spectral study. All the designed hybrids were evaluated for their in vitro anticancer activity against a panel of three human cancer cell lines viz SK-MEL-2(melanoma), HL-60 (leukemia) and MCF-7 using MTT assays method. Most of the synthesized compounds exhibited promising anticancer activity with the some compounds having GI50 values similar to that of the Adriamycin. The compounds 7k, 7l, 7b, and 7a were found to be the most promising in this study. A computational study of synthesized compounds 7(a–l) was performed for prediction of ADMET. The absorption, distribution, metabolism, excretion and Toxicity (ADMET) properties of all compounds were predicted using Qikprop v3.5 (Schrödinger LLC

Facile synthesis of novel coumarin derivatives, antimicrobial analysis, enzyme assay, docking study, ADMET prediction and toxicity study

The work reports the synthesis under solvent-free condition using the ionic liquid [Et3NH][HSO4] as a catalyst of fifteen novel 3-((dicyclohexylamino)(substituted phenyl/heteryl)-methyl)-4-hydroxy-2H-chromen-2-onederivatives 4a–o as potential antimicrobial agents. The structures of the synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, mass spectral studies and elemental analyses. All the synthesized compounds were evaluated for their in vitro antifungal and antibacterial activity. The compound 4k bearing 4-hydroxy-3-ethoxy group on the phenyl ring was found to be the most active antifungal agent. The compound 4e bearing a 2,4-difluoro group on the phenyl ring was found to be the most active antibacterial agent. The mode of action of the most promising antifungal compound 4k was established by an ergosterol extraction and quantitation assay. From the assay it was found that 4k acts by inhibition of ergosterol biosynthesis in C. albicans. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds to the active site of lanosterol 14α-demethylase, which suggests that the tested compounds inhibit the synthesis of this enzyme. The synthesized compounds were analyzed for in silico ADMET properties to establish oral drug like behavior and showed satisfactory results. To establish the antimicrobial selectivity and safety, the most active compounds 4e and 4k were further tested for cytotoxicity against human cancer cell line HeLa and were found to be non-cytotoxic in nature. An in vivo acute oral toxicity study was also performed for the most active compounds 4e and 4k and results indicated that the compounds are non-toxic.S

Ultrasound Mediated One-Pot, Three Component Synthesis, Docking and ADME Prediction of Novel 5-Amino-2-(4-chlorophenyl)-7-Substituted Phenyl-8,8a-dihydro-7H-(1,3,4)thiadiazolo(3,2-α)pyrimidine-6-carbonitrile Derivatives as Anticancer Agents

Herein, we report an environmentally friendly, rapid, and convenient one-pot ultrasound-promoted synthesis of 5-amino-2-(4-chlorophenyl)-7-substituted phenyl-8,8a-dihydro-7H-(1,3,4)thiadiazolo(3,2-α)pyrimidine-6-carbonitrile derivatives. The in-vitro anticancer activities of these compounds were evaluated against four human tumor cell lines. Among all the synthesized derivatives, compound 4i, which has substituent 3-hydroxy-4-methoxyphenyl is found to have the highest GI50 value of 32.7 μM, 55.3 μM, 34.3 μM, 28.9 μM for MCF-7, K562, HeLa and PC-3 cancer cell lines respectively. A docking study of the newly synthesized compounds were performed, and the results showed good binding mode in the active site of thymidylate synthase enzyme. ADME properties of synthesized compounds were also studied and showed good drug like propertiesThe authors are thankful to the Fatima Rafiq Zakaria Chairman Maulana Azad Educational Trust and Zahid Zaheer, Incharge Principal, Y.B. Chavan College of Pharmacy, Rafiq Zakaria Campus, Aurangabad 431 001 (M.S.), India for providing the laboratory facility. In vitro SRB assay for anti-cancer activity evaluation of drugs was performed at Anti-Cancer Drug screening facility (ACDSF) at ACTREC, Tata Memorial Centre, Navi Mumbai and the authors are greatful to Jyoti Kode for her cooperation in in-vitro studiesS

Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals

Although required for many fundamental immune processes, ranging from self-tolerance to pathogen immunity, interleukin (IL)-2 production is transient, and the mechanisms underlying this brevity remain unclear. These studies reveal that helper T cell IL-2 production is limited by a classic negative feedback loop that functions autonomously or in collaboration with other common γ chain (IL-4 and IL-7) and IL-6/IL-12 family cytokines (IL-12 and IL-27). Consistent with this model for cytokine-dependent regulation, they also demonstrate that the inhibitory effect can be mediated by several signal transducer and activator of transcription (STAT) family transcription factors, namely STAT5, STAT4, and STAT6. Collectively, these findings establish that IL-2 production is limited by a network of autocrine and paracrine signals that are readily available during acute inflammatory responses and, thus, provide a cellular and molecular basis for its transient pattern of expression

Microwave-assisted facile synthesis, anticancer evaluation and docking study of N-((5-(substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl) benzamide derivatives

In the present work, 12 novel Schiff’s bases containing a thiadiazole scaffold and benzamide groups coupled through appropriate pharmacophore were synthesized. These moieties are associated with important biological properties. A facile, solvent-free synthesis of a series of novel 7(a–l) N-((5-(substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl) benzamide was carried out under microwave irradiation. Structures of the synthesized compounds were confirmed by IR, NMR, mass spectral study and elemental analysis. All the synthesized hybrids were evaluated for their in vitro anticancer activity against a panel of four human cancer cell lines, viz. SK-MEL-2 (melanoma), HL-60 (leukemia), HeLa (cervical cancer), MCF-7 (breast cancer) and normal breast epithelial cell (MCF-10A) using 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method. Most of the synthesized compounds exhibited promising anticancer activity, showed comparable GI50 values comparable to that of the standard drug Adriamycin. The compounds 7k, 7l, 7b, and 7a were found to be the most promising anticancer agents in this study. A molecular docking study was performed to predict the probable mechanism of action and computational study of the synthesized compounds 7(a–l) was performed to predict absorption, distribution, metabolism, excretion and toxicity (ADMET) properties, by using QikProp v3.5 (Schrödinger LLC). The results showed the good oral drug-like behavior of the synthesized compounds 7(a–l).: The authors are thankful to Fatima Rafiq Zakaria, Chairman, Maulana Azad Educational Trust and the Principal, Y.B. Chavan College of Pharmacy, Rafiq Zakaria Campus, Aurangabad 431001 (MS), India for providing the laboratory facility. The authors are grateful to Anti-Cancer Drug screening facility (ACDSF) at ACTREC, Tata Memorial Centre, Navi Mumbai for performing in vitro MTT assay for anti-cancer evaluation of our synthesized derivatives.S

Strange Behaviour of Transport Properties in Novel Metal Thiocyanate Based Ionic Liquids

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUGThe following are the Supplementary data to this article: https://ars.els-cdn.com/content/image/1-s2.0-S0167732221018882-mmc1.docx[Abstract] In a previous paper some of us presented the structure and some properties of a new family of ionic liquids, ILs, with a common cation, 1-butyl-3-methyl imidazolium (the popular [C4C1Im]⁺ or [BMIM]⁺) and a variety of anions based in thiocyanate (SCN)¯: one reference sample and ten with anionic metal complexes of different valences: Al¹¹¹, Mn¹¹, Fe¹¹, Cr¹¹¹, Ni¹¹, Hg¹¹, Zn¹¹, Co¹¹ and Cu¹, resulting, respectively, [BMIM](SCN), [BMIM]₃ Al(SCN)₆, [BMIM]₄ Mn(SCN)₆, [BMIM]₃ Fe(SCN)₆, [BMIM]₃ Cr(SCN)₆, [BMIM]₄ Ni(SCN)₆, [BMIM]₂ Hg(SCN)₄, [BMIM]₂ Zn(SCN)₄, [BMIM]₂ Co(SCN)₄ and [BMIM]₃ Cu(SCN)₄. In this paper we show experimental measurements of electrical conductivity of these ILs in a broad temperature range (about 90 K). Viscosity has been measured for six compounds in a wide temperature range. In addition, the diffusion coefficient for both ions forming the IL has been measured for some of the samples using NMR-Dosy technique. In spite of being very similar compounds from a chemical point of view, they present very different transport property values. Thus, viscosity varies more than two orders of magnitude among those metal thiocyanate ILs, being the highest for the compound with Al and the lowest for that with Hg. Moreover, differences between ionic conductivity and diffusion coefficient values extend more than one order of magnitude among the thiocyanate ILs. These three properties will be related in pairs, thus through Walden’s rule we compare molar conductivity and fluidity, while using Kohlrausch’s law and Nerst-Einstein equation molar conductivity and diffusion coefficient are related. Also, diffusion coefficient and fluidity (the inverse of viscosity) are compared by means of Stokes-Einstein relationship. In addition, we calculate the Laity interionic friction coefficients for both anions of the IL with Hg. Finally, a theoretical model is suggested to explain all the experimental evidences reported.We acknowledge the financial support of Ministerio de Economía y Competitividad MINECO) (MAT2017-86109-P and MAT2017-89239-C2-(1.2)-P); and Xunta de Galicia (AGRU 015/11. GRC ED431C 2016/001 and ED431D 2017/06). All these research projects were partially supported by FEDER. Also, D.A. acknowledges Gil Dávila Foundation for his postgraduate grant. Funding for open access charge: Universidade da Coruña/CISUG.Xunta de Galicia; ED431C 2016/001Xunta de Galicia; ED431D 2017/06https://ars.els-cdn.com/content/image/1-s2.0-S0167732221018882-mmc1.doc

Analysis of the evolution of hake (Merluccius hubbsi and Merluccius australis) catch and effort by Spanish vessels operating in the Patagonian shelf area since the beginning of this industrial fishery

The hake fishery (Merluccius hubbsi and Merluccius australis) is one of the most important ones for Spanish vessels operating in the Southwest Atlantic. Both species are widely distributed along the Patagonian shelf, although M. australis occupies mainly more southern waters. This paper presents a historical review of fishery data on the Spanish fishing fleet operating in the SW Atlantic collected and collated during the EC Study Project 99/016 “Data collection for stock assessment of two hakes (Merluccius hubbsi and M. australis) in International and Falkland waters of the SW Atlantic”, in order to analyse the evolution of catch and effort in the hake fishery since 1983 to 2000. Data on landings and effort by Spanish vessels from 1983 onwards were utilised to study trends and shifts within the fishery. These data were provided by Asociación Nacional de Armadores de Buques Congeladores de Pesca de Merluza (ANAMER), the most important Spanish ship-owners fishing association operating in distant fishing grounds. Catch and effort data collected by observer’s programmes carried out by Instituto Español de Oceanografía (IEO) and the Falkland Islands Government Fisheries Department (FIGFD), as well as by observers provided by the project were used to estimate CPUE by area and season.The data included landings in kgs by commercial size category of hake (both species together) and effort made by vessels appertaining to ANAMER in number of fishing days and number of vessels by vessel size category. Conversion factors obtained by scientific observers onboard of these vessels were used to obtain the whole catch from landings. Total effort of the Spanish fleet was estimated from ANAMER logbooks, assuming a similar pattern for the whole fleet and taking into account the different ratio of ANAMER fleet compared to the total Spanish fleet. An increase of the catches and effort was observed from 1983 to a maximum in 1990 coinciding with the closure of Namibian fisheries. After that, catches and effort decreased corresponding to the development of the Greenland halibut fishery in the NW Atlantic, until its stabilisation from 1993. CPUE showed different patterns of fishing activity by area and season

Enhancing non-profit engagement: the extended model of webpage engagement and adoption for strategic management

This paper examines the study of Non-Profit Organization’s (NPOs’) webpages through the Strategic Online Communication Approach (SOCA) context to underpin public engagement. Although it can be argued that social networking sites such as Facebook or Twitter have a significant role in interactive online engagement, it is often webpages that have the critical role in creating engagement in the initial (and arguably most important) stage of opening dialog. In the SOCA context NPOs’ webpages need to be strategically planned and aligned with the NPOs goals and targeted to various stakeholders such as the general public, volunteers and donors. In general terms, this research resulted in a sequential model called EMEA (Extended Model of Webpages Engagement and Adoption) with three levels (information, interaction, and action). The EMEA model shows the efficiency and maturity of the webpages, indicating the level of engagement that should be possible, to therefore improve relationships with the public and obtain better results. Results show that the more ‘ways to help’ an NPO presents on its webpage, the greater the level of potential engagement (as different options to collaborate, convey trustworthy information, and control content are evident). Finally, this research showed that the greater engagement achieved by NPOs, the better the likely results and therefore the effective application of EMEA can explain and even predict success for NPOs. This paper only addresses web pages, and therefore further research is needed to clarify the role of Social Networking Sites (SNS) for high interactivity. Secondly, although EMEA is able to explain and even predict the levels of engagement, it is not evident that it necessarily occurs. Finally, although EMEA is applied correctly, it does not guarantee that NPOs are managing communication in the context of SOCA, since a multi-channel online strategy is required

Metagenomic characterization of swine slurry in a North American swine farm operation

Abstract Modern day large-scale, high-density farming environments are inherently susceptible to viral outbreaks, inadvertently creating conditions that favor increased pathogen transmission and potential zoonotic spread. Metagenomic sequencing has proven to be a useful tool for characterizing the microbial burden in both people, livestock, and environmental samples. International efforts have been successful at characterizing pathogens in commercial farming environments, especially swine farms, however it is unclear whether the full extent of microbial agents have been adequately captured or is representative of farms elsewhere. To augment international efforts we performed metagenomic next-generation sequencing on nine swine slurry and three environmental samples from a United States of America (U.S.A.) farm operation, characterized the microbial composition of slurry, and identified novel viruses. We assembled a remarkable total of 1792 viral genomes, of which 554 were novel/divergent. We assembled 1637 Picobirnavirus genome segments, of which 538 are novel. In addition, we discovered 10 new viruses belonging to a novel taxon: porcine Statoviruses; which have only been previously reported in human, macaques, mouse, and cows. We assembled 3 divergent Posaviruses and 3 swine Picornaviruses. In addition to viruses described, we found other eukaryotic genera such as Entamoeba and Blastocystis, and bacterial genera such as Listeria, Treponema, Peptoclostridium and Bordetella in the slurry. Of these, two species Entamoeba histolytica and Listeria monocytogenes known to cause human disease were detected. Further, antimicrobial resistance genes such as tetracycline and MLS (macrolide, lincosamide, streptogramin) were also identified. Metagenomic surveillance in swine fecal slurry has great potential for novel and antimicrobial resistant pathogen detection