Neoflavonoids as Inhibitors of HIV-1 Replication by Targeting the Tat and NF-kB Pathways

Twenty-eight neoflavonoids have been prepared and evaluated in vitro against HIV-1. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase reporter gene. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Seven 4-phenylchromen-2-one derivatives showed HIV transcriptional inhibitory activity but only the phenylchrome-2-one 10 inhibited NF- B and displayed anti-Tat activity simultaneously. Compounds 10, 14, and 25, inhibited HIV replication in both targets at concentrations <25 M. The assays of these synthetic 4-phenylchromen-2-ones may aid in the investigation of some aspects of the anti-HIV activity of such compounds and could serve as a scaffold for designing better anti-HIV compounds, which may lead to a potential anti-HIV therapeutic dru

Novel compound shows in vivo anthelmintic activity in gerbils and sheep infected by Haemonchus contortus

8 páginas, 2 figuras, 2 tablas.The control of gastrointestinal nematodes in livestock is becoming increasingly difficult due to the limited number of available drugs and the rapid development of anthelmintic resistance. Therefore, it is imperative to develop new anthelmintics that are effective against nematodes. Under this context, we tested the potential toxicity of three compounds in mice and their potential anthelmintic efficacy in Mongolian gerbils infected with Haemonchus contortus. The compounds were selected from previous in vitro experiments: two diamine (AAD-1 and AAD-2) and one benzimidazole (2aBZ) derivatives. 2aBZ was also selected to test its efficacy in sheep. In Mongolian gerbils, the benzimidazole reduced the percentage of pre-adults present in the stomach of gerbils by 95% at a dose of 200 mg/kg. In sheep, there was a 99% reduction in the number of eggs shed in faeces after 7 days at a dose of 120 mg/kg and a 95% reduction in the number of worm adults present in the abomasum. In conclusion, 2aBZ could be considered a promising candidate for the treatment of helminth infections in small ruminants. © 2022, The Author(s).Financial support came from MINECO: RETOS (AGL2016-79813-C2-1R/2R) and MICINN/AEI (PID2020- 119035RB-100). EVG was funded by FPU17/00627, FPU17/05346; VCGA, MAB, MCP and LGP are recipients of Junta de Castilla y León (JCyL) (LE082-18, LE051-18, LE135-19, LE096-20, respectively) and MMV by the Spanish “Ramon y Cajal” Programme (Ministerio de Economía y competitividad; MMV, RYC-2015-18368).Peer reviewe

3-Phenylcoumarins as Inhibitors of HIV-1 Replication

We have synthesized fourteen 3-phenylcoumarin derivatives and evaluated their anti-HIV activity. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase gene as reporter. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Six compounds displayed NF-κB inhibition, four resulted Tat antagonists and three of them showed both activities. Three compounds inhibited HIV replication with IC50 values < 25 μM. The antiviral effect of the 4-hydroxycoumarin derivative 19 correlates with its specific inhibition of Tat functions, while compound 8, 3-(2-chlorophenyl)coumarin, seems to act through a mechanism unrelated to the molecular targets considered in this research

Anthelmintic activity of aminoalcohol and diamine derivatives against the gastrointestinal nematode Teladorsagia circumcincta

11 páginas, 5 figuras, 4 tablas.Gastrointestinal nematodes (GIN) infections are a serious problem in livestock production due to the great economic losses they cause. Their control is increasingly difficult because of the rapid development of drug resistance and the limited number of available drugs. Therefore, this study evaluated 18 aminoalcohol and 16 diamine derivatives against eggs, first and third stage larvae from a susceptible and a resistant isolate of Tela-dorsagia circumcincta collected from sheep. The effectiveness of the in vitro anthelmintic activity of the com-pounds was evaluated using three different procedures: Egg Hatch Test (EHT), Larval Mortality Test (LMT) and Larval Migration Inhibition Test (LMIT). Those compounds with activities higher than 90 % in the initial screening at 50 μM were selected to determine their half maximal effective concentration (EC50). In parallel, cytotoxicity assays were conducted on Caco2 and HepG2 cell lines to calculate Selectivity Indexes (SI) for each compound. The diamine 30 presented the best results in preventing egg hatching, displaying the lowest EC50 value (1.01 ±0.04 μM) of all compounds tested and the highest SI (21.21 vs. Caco-2 cells). For the LMIT, the diamine 34 showed the highest efficacy, with EC50 values of 2.67 ±0.08 and 3.02 ±0.09 μM on the susceptible and resistant isolate of the parasite, respectively.We are grateful to Dave Bartley, from Moredun Research Institute for providing the triple-resistant isolate of T. circumcincta. RE thank the RICET contract (E07D401988BR) EC Programs. Financial support came from MINECO: RETOS (AGL2016-79813-C2-1R/2R) and Junta de Castilla y León (JCyL) co-financed by FEDER, UE (LE020P17). EVG was funded by FPU16/03536; JV, VCGA and MAB are recipients of Junta de Castilla y Leon and European Social Found (ESF)’s Fellowships Scheme for Doctoral Training Programs. (JCYL-USAL35B, LE082-18, LE051-18, respectively) and MMV by the Spanish “Ramon y Cajal” Programme (Ministerio de Economía y Competitividad; RYC-2015-18368).Peer reviewe

Los minerales de la arcilla en los ambientes deposicionales de la fm Escucha (Albiense medio, Sistema Ibérico)

Plana F., Queralt I., Quexol X., Fernández Turiel J. L., San Feliú T., Los minerales de la arcilla en los ambientes deposicionales de la fm Escucha (Albiense medio, Sistema Ibérico). Boletín de la Sociedad Española de Mineralogía, ISSN 0210-0658, 1992, 15 (1): 104-107.The Escucha Fm. (Middle Albian, Iberian Range, NE Spain) consists of alternating coal bearing and fine siliciclastic deposits up to 550 m thick. During Albian times fluvio-deltaic, swamp and marine environments prevailed in this area. Paleoenvironmental modelling was realized from sedimentology data in an earlier study (Querol, 1990) and allow us to distinguish five depositional zones (a/fluvio- deltaic plain, b/peat bog flat, c/brackish water swamp belt, d/delta front, e/prodelta) in order to recognize different mineral assemblages. Mineralogical analysis in the whole rock and the clay fraction from 49 samples of sediments interbedded in coal sequences were performed by X-ray diffraction means. A semiquantitative estimation of mineral contents in the whole rock and of the clay minerals in fine fraction was obtained following the criterion of Chung (1974) and Inglés & Anadón (1991). The mineral assemblages in the rocks studied are formed mainly by quartz and kaolinite. Substantial amounts of illite and mixed layer illite/smectite are present, and it is also possible occasionally to identify feldspars, calcite, gypsum, jarosite, hematite and pyrite. There is no correlation between the mineral features of assemblages and the location of the samples in the vertical profiles. The obtained results show a relationship between mineral distribution and the different depositional zones. In this sense, it can be regarded that the amount of the mixed layer illite/smectite increases to the prodelta sediments, the ranges of quartz distribution and illite crystallinity spreading to the fluvio-deltaic deposits, and the kaolinite/illite ratio is lower in prodeltaic environment, reflecting the changes in the physico-chemical conditions of deposition.Peer reviewe

Eudesmanolides and other terpenoids from Trattinickia rhoifolia

De la resina de Trattinickia rhoifolia fueron aisladas tres eudesmanolidas, 8ß,9a-dihidroxieudesma-4(15),7(11)-dien-12,8-olida (1), 8a,9a-epoxieudesma-4 (15),7(11)-dien-12,8-olida (2), y 8,8’-bis[eudesma-4(15),7(11)-dien-12,8ß-olida] (3), y diecisiete compuestos conocidos. Las estructuras de los compuestos fueron elucidadas mediante la interpretación de los datos espectroscópicos y el análisis del modelaje [email protected] eudesmanolides, 8ß,9a-dihydroxyeudesma-4(15),7(11)-dien-12,8-olide (1), 8a,9a-epoxyeudesma-4(15), 7(11)-dien-12,8-olide (2), and 8,8'-bis[eudesma-4 (15),7(11) -dien-12,8ß-olide] (3), together with seventeen known compounds were isolated from the resin of Trattinickia rhoifolia. The structures of the compounds were elucidated by spectroscopic data interpretation and molecular modeling analysis

9-epi-labdane diterpenoids from Nolana rostrata var. rostrata

Two new 9-epi-labdane diterpenes 2α,3α,9β-trihydroxy-9-epi-labd- 13(E)-ene-15-oic acid and 2α,3α,9β-trihydroxy-9-epi-labd-13(Z)-ene-15-oic acid and the known flavonoid 5,3',4'-trihydroxy-3,7-dimetoxy-quercetin were isolated from the aerial parts of Nolana rostrata vat. rostrata

Methyl psilalate: A new antimicrobial metabolite from Psila boliviensis

Psila boliviensis (Wedd.) Cabr. yielded a new phenylpropanoid, named methyl psilalate. The structure was established by means of standard spectroscopic techniques. The microbiological evaluation of the compound revealed antibacterial activity against Gram-positive and Gram-negative bacteria

Inotropic activity of hydroindene amidinohydrazones

Several hydroindenic derivatives (7a-methyl-2,3,5,6,7,7a-hexahydro-1H-indenes), bearing an amidinohydrazone at C-5 and different moieties at C-1, have been synthesized and evaluated for their inotropic and chronotropic effects on right- and left-guinea-pig-atria activity. Three of them showed the same profile as digoxin, although with lower potency. The effect on Na(+),K(+)-ATPase (NKA) was also evaluated for these three compounds, observing that two of them, with the same absolute configuration as natural cardenolides, are also NKA inhibitors, while the compound with the opposite configuration lacks such an effect. More interestingly, both active compounds act without affecting the cardiac rhythm. This could be related to the selective inhibition of the human alpha2beta1 isozyme (associated with the inotropic effect) with respect to the alpha1beta1 isozyme (associated with the maintenance of basal ionic levels in the cell and the toxic effect of cardenolides)