The uses of ethyl 2-(1H-benzo[D]imidazol-2-yl)acetate to synthesis pyrazole, thiophene, pyridine and coumarin derivatives with antitumor activities

In the present work, the ethyl 2-(1H-benzo[d]imidazol-2-yl)acetate (3) was subjected to a series of  heterocyclization reactions through its reaction with different chemical reagents. The resulting molecules were thiophene, pyrazole, coumarin derivatives incorporated benzo[d]imidazole moiety. All the synthesized compounds were determined by elemental analysis, 1H NMR, 13C NMR, and MS. The antitumor evaluations of the newly synthesized products toward the three cancer cell lines MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), and SF-268 (CNS cancer) showed that compounds 5a, 9b, 9c, 17, 23b and 38 were of the highest potencies among the synthesized compounds.               KEY WORDS: Oxobutanamide, Thiophene, Pyrazole, Pyran, Pyridine Bull. Chem. Soc. Ethiop. 2018, 32(3), 541-557.DOI: https://dx.doi.org/10.4314/bcse.v32i3.1

Novel synthesis of pyran-3-hydrazide derivatives and their uses to the synthesis hydrazide-hydrazone, pyrazole and thiazole derivatives with anticancer activities

ABSTRACT. The multi-component reaction of ethyl acetoacetate with each of malononitrile (3) benzaldehyde (1) in ethanol containing triethylamine gave the ethyl 6-amino-5-cyano-2-methyl-4-phenyl-4H-pyran-3-carboxylate (4). The latter compound reacted with hydrazine hydrate to give the hydrazide derivative 6. Compound 6 underwent a series of hetero-cyclization reactions to give pyrzole, hydraide-hydrazone, thiazole derivatives. The produced compounds tested against cancer cell lines six cancer cell lines and showed that compounds 8b, 10b, 11a, 17a, 21 and 24a were the most cytotoxic compounds. Further tests of the latter compounds toward the five tyrosine kinases and Pim-1 kinase showed that compounds 10b, 21 and 24a were the most potent of the tested compounds and compounds 10a, 11a and 17a were of the highest inhibitions toward Pim-1 kinase. The high inhibitions of most of the tested compounds toward the selected cancer cell lines and the tyrosine kinases encourage for future work to be done.                     KEY WORDS: Hydrazide, Thiophene, Pyrazole, Pyran, Cytotoxicity, Tyrosine kinases   Bull. Chem. Soc. Ethiop. 2021, 35(3), 573-586.  DOI: https://dx.doi.org/10.4314/bcse.v35i3.

Discovery of new thiophene, pyrazole, isoxazole derivatives as antitumor, c-Met, tyrosine kinase and Pim-1 kinase inhibitors

The reaction of cyclohexan-1,3-dione (1) with ethyl orthoformate (2) in acetic acid gave the 2-(ethoxymethylene)cyclohexane-1,3-dione (3). The latter compound was used for further heterocyclization reactions to give thiophene, pyrazole and pyran derivatives. The cytotoxicity of the newly synthesized compound against the six cancer cell lines NUGC, DLDI, HA22T, HEPG2, HONE1 and MCF showed that compounds 5, 10c, 10d, 13b, 14a, 18b, 18d, 18e and 20b were the most potent compounds. On the other hand, the toxicity of these compounds against shrimp larvae indicated that compounds 7a, 10c, 13b, 14a, 18b and 18d were non toxic against the tested organisms. Inhibition of the most potent compounds towards the tyrosine kinases c-kit, FIT-3, Vascular Endothelial Growth Factor Receptor (VEGFR)-2, Estimated Glomerular Filtration Rate (EGFR) and Platelet-Derived Growth Factor Receptor (PDGFR) revealed that compounds 5, 10c, 10d, 13b, 18b, 18d, 18e and 20b were of the highest inhibitory effect. The Pim-1 kinase test revealed that compounds 10d, 18b and 20b were of the highest inhibitory effect. In addition, the c-Met enzymatic activities showed that compounds 10c, 10d, 18b, 18e, 19 and 20b showed higher potencies against c-Met kinase than the reference foretinib. On the other hand, compounds 7a, 7b, 10d, 13a, 13b, 14a, 14b, 16a, 16b, 17, 18a-f, 19 and 20 showed higher inhibition towards PC-3 cell line than the reference SGI-1776. Compounds 10c and 18b were of common potencies and their molecular docking was described.               KEY WORDS: Cyclohexane 1,3-dione, Pyrazole, Thiophene, Cytotoxicity, Tyrosine kinases Bull. Chem. Soc. Ethiop. 2018, 32(2), 285-308.DOI: https://dx.doi.org/10.4314/bcse.v32i2.

Simulations of a lattice model of two-headed linear amphiphiles: influence of amphiphile asymmetry

Using a 2D lattice model, we conduct Monte Carlo simulations of micellar aggregation of linear-chain amphiphiles having two solvophilic head groups. In the context of this simple model, we quantify how the amphiphile architecture influences the critical micelle concentration (CMC), with a particular focus on the role of the asymmetry of the amphiphile structure. Accordingly, we study all possible arrangements of the head groups along amphiphile chains of fixed length $N=12$ and 16 molecular units. This set of idealized amphiphile architectures approximates many cases of symmetric and asymmetric gemini surfactants, double-headed surfactants and boloform surfactants. Consistent with earlier results, we find that the number of spacer units $s$ separating the heads has a significant influence on the CMC, with the CMC increasing with $s$ for $s<N/2$. In comparison, the influence of the asymmetry of the chain architecture on the CMC is much weaker, as is also found experimentally.Comment: 30 pages, 17 fgure

Simulations of a lattice model of two-headed linear amphiphiles: influence of amphiphile asymmetry

Using a 2D lattice model, we conduct Monte Carlo simulations of micellar aggregation of linear-chain amphiphiles having two solvophilic head groups. In the context of this simple model, we quantify how the amphiphile architecture influences the critical micelle concentration (CMC), with a particular focus on the role of the asymmetry of the amphiphile structure. Accordingly, we study all possible arrangements of the head groups along amphiphile chains of fixed length $N=12$ and 16 molecular units. This set of idealized amphiphile architectures approximates many cases of symmetric and asymmetric gemini surfactants, double-headed surfactants and boloform surfactants. Consistent with earlier results, we find that the number of spacer units $s$ separating the heads has a significant influence on the CMC, with the CMC increasing with $s$ for $s<N/2$. In comparison, the influence of the asymmetry of the chain architecture on the CMC is much weaker, as is also found experimentally.Comment: 30 pages, 17 fgure

A Monitoring System for Crimean Congo Hemorrhagic Fever Epidemiology Studies in Afghanistan

In the last few years, tick-borne diseases have been reported as a resurging in the Middle East. Crimean-Congo hemorrhagic fever (CCHF) is endemic in the Middle East, including Turkey, Iran, Afghanistan and Pakistan. Recent studies have explored the causal link between environmental and disease incidence patterns by correlating remote sensing indicators (surface temperature, rainfall, and vegetation indices of plant photosynthetic activity) with spatially explicit epidemiological data. We combined the monitoring of environmental data at monthly temporal resolutions with available reports of confirmed CCHF cases to identify the environmental properties of endemic regions and quantify those properties to CCHF risk. We also conducted a sero-prevalence survey in a sample of households (human and animal specimens) in 9 villages in Engil district surrounding Herat province, in western Afghanistan. We present analysis results from our study villages and validate the associated environmental conditions as predictive for human disease occurrences. Risk prediction is critical for anticipating the type and potential impact of disease threats for timely response action

Cities’ role in mitigating United States food system greenhouse gas emissions

Current trends of urbanization, population growth, and economic development have made cities a focal point for mitigating global greenhouse gas (GHG) emissions. The substantial contribution of food consumption to climate change necessitates urban action to reduce the carbon intensity of the food system. While food system GHG mitigation strategies often focus on production, we argue that urban influence dominates this sector’s emissions and that consumers in cities must be the primary drivers of mitigation. We quantify life cycle GHG emissions of the United States food system through data collected from literature and government sources producing an estimated total of 3800 kg CO2e/capita in 2010, with cities directly influencing approximately two-thirds of food sector GHG emissions. We then assess the potential for cities to reduce emissions through selected measures; examples include up-scaling urban agriculture and home delivery of grocery options, which each may achieve emissions reductions on the order of 0.4 and ∼1% of this total, respectively. Meanwhile, changes in waste management practices and reduction of postdistribution food waste by 50% reduce total food sector emissions by 5 and 11%, respectively. Consideration of the scale of benefits achievable through policy goals can enable cities to formulate strategies that will assist in achieving deep long-term GHG emissions targets

Global genetic diversity of var2csa in Plasmodium falciparum with implications for malaria in pregnancy and vaccine development

Malaria infection during pregnancy, caused by the sequestering of Plasmodium falciparum parasites in the placenta, leads to high infant mortality and maternal morbidity. The parasite-placenta adherence mechanism is mediated by the VAR2CSA protein, a target for natural occurring immunity. Currently, vaccine development is based on its ID1-DBL2Xb domain however little is known about the global genetic diversity of the encoding var2csa gene, which could influence vaccine efficacy. In a comprehensive analysis of the var2csa gene in >2,000 P. falciparum field isolates across 23 countries, we found that var2csa is duplicated in high prevalence (>25%), African and Oceanian populations harbour a much higher diversity than other regions, and that insertions/deletions are abundant leading to an underestimation of the diversity of the locus. Further, ID1-DBL2Xb haplotypes associated with adverse birth outcomes are present globally, and African-specific haplotypes exist, which should be incorporated into vaccine design

Ispitivanje antidepresivnog, sedativnog i analgetskog djelovanja novih fuzioniranih derivata tiofena

This study was aimed at the synthesis of fused benzothiophene derivatives containing heterocyclic moiety. The reaction of the tetrahydrobenzo[b]thiophene derivatives 1a,b with ethoxycarbonylisothiocyanate afforded the thiourea derivatives 2a,b. Cyclization of the latter products gave the annulated benzo[b]thienopyrimidine derivatives 3a,b. Compounds 2a,b and 3a underwent a series of heterocyclization reactions through the reaction with some chemical reagents to give the new benzo[b]thienopyrimidine derivatives 5a,b to 8a-c. Also, this work was extended to study the potential role of the novel synthesized thiourea derivative 2a and benzo[b]thienopyrimidine derivatives 3a, 5b, 6a and 8b as antidepressant, sedative or analgesic agents at two doses (15 or 30 mg kg1 body mass). Some compounds (2a, 3a and 5b) showed mild antidepressant activity in the forced-swimming test. No compound showed sedative effect. Visceral pain evoked by i.p. injection of acetic acid in mice was significantly inhibited by all compounds at a high doses.U radu je opisana sinteza fuzioniranih derivata benzotiofena koji sadrže heterociklički ostatak bitan za farmakološko djelovanje. Tiourea derivati 2a,b dobiveni su reakcijom derivata tetrahidrobenzo[b]tiofena 1a,b s etoksikarbonilizotiocijanatom. Iz njih su dalje priređeni anulirani derivati benzo[b]tienopirimidina 3a,b. Spojevi 2a,b i 3a prevedeni su reakcijama heterociklizacije u benzo[b]tienopirimidine 5a,b-8a-c. Ispitivano je antidepresivno, sedativno i analgetsko djelovanje novosintetiziranih derivata tiouree 2a i benzo[b]tienopirimidina 3a, 5b, 6a i 8b u dvije doze (15 ili 30 mg kg1 tjelesne mase). Spojevi 2a, 3a i 5b pokazali su blago antidepresivno djelovanje u testu forsiranog plivanja, dok sedativni učinak nije pokazao niti jedan ispitivani spoj. Visceralna bol inducirana i.p. injekcijom octene kiseline u miševa značajno je inhibirana sa svim spojevima, ali u visokim dozama

Green Infrastructure in the Space of Flows: An Urban Metabolism

Recent research demonstrates that urban metabolism studies hold ample scope for informing more sustainable urban planning and design. The assessment of the resource flows that are required to sustain the growth and maintenance of cities can allow gaining a clear picture of how cities operate to comply with environmental performance standards and to ensure that both human and ecosystem health are preserved. Green infrastructure (GI) plays a key role in enhancing both cities’ environmental performance and health. For example, GI interventions mitigate the Urban Heat Island effect (improved thermal comfort), reduce particulate matter concentration (healthier air quality), and sequestrate and store atmospheric carbon (climate change mitigation). Research on ecosystem services and the application of the concept in urban planning provides a growing evidence base that an understanding of provisioning and regulating services can facilitate more environmentally informed GI planning and design. The contribution of GI in enhancing human health and psychological wellbeing is also evidenced in recent studies valuing both material and immaterial benefits provided by urban ecosystems, including cultural ecosystem services. Therefore, the use of ecosystem service frameworks can help reveal and quantify the role of GI in fostering both urban environmental quality and the wellbeing of human populations. However, there remains little discussion of how health and wellbeing aspects can be integrated with environmental performance objectives. In this chapter, urban metabolism thinking is proposed as a way forward, providing analytical tools to inform environmentally-optimized strategies across the urban scales. Opportunities to foster integrated urban metabolism approaches that can inform more holistic GI planning are discussed. Finally, future research avenues to incorporate the multiple dimensions of human health and wellbeing into urban metabolism thinking are highlighted