HD 213258: a new rapidly oscillating, super-slowly rotating, strongly magnetic Ap star in a spectroscopic binary

We report about HD 213258, an Ap star that we recently identified as presenting a unique combination of rare, remarkable properties. Our study of this star is based on ESPaDOnS Stokes I and V data obtained at 7 epochs spanning a time interval slightly shorter than 2 years, on TESS data, and on radial velocity measurements from the CORAVEL data base. We confirm that HD 213258 is definitely an Ap star. We found that, in its spectrum, the Fe II {\lambda}6149.2 {\AA} line is resolved into its two magnetically split components. The mean magnetic field modulus of HD 213258, ~ 3.8 kG does not show significant variations over ~2 years. Comparing our mean longitudinal field determinations with a couple of measurements from the literature, we show that the stellar rotation period must likely be of the order of 50 years, with a reversal of the field polarity. Moreover, HD 213258 is a rapidly oscillating Ap (roAp) star, in which high overtone pulsations with a period of 7.58 min are detected. Finally, we confirm that HD 213258 has a mean radial velocity exceeding (in absolute value) that of at least 99% of the Ap stars. The radial velocity shows low amplitude variations, which suggests that the star is a single-line spectroscopic binary. It is also a known astrometric binary. While its orbital elements remain to be determined, its orbital period likely is one of the shortest known for a binary roAp star. Its secondary is close to the borderline between stellar and substellar objects. There is a significant probability that it may be a brown dwarf. While most of the above-mentioned properties, taken in isolation, are observed in a small fraction of the whole population of Ap stars, the probability that a single star possesses all of them is extremely low. This makes HD 213258 an exceptionally interesting object that deserves to be studied in detail in the future.Comment: Accepted for publication in A&A; 6 pages, 4 figure

Інгібування ксантиноксидази похідними піразолону, що містять фрагмент 4-(фуран-2-іл)бензойної кислоти

The pyrazolone-based 4-(furan-2-yl)benzoic acids have been synthesized and studied as xanthine oxidase inhibitors. This enzyme is one of the therapeutic targets for the treatment of hyperuricemia and related diseases. The compounds studied have found to exhibit low micromolar IC50 values relative to the enzyme in vitro, depending on substituents in position 3 of the pyrazolone ring. However, the inhibitory effects observed are reduced in the presence of bovine serum albumin or Tween-80. Among the pyrazolone derivatives synthesized, 4-(5-((3-methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)methyl)furan-2-yl)benzoic acid has been found to be the most potent inhibitor of xanthine oxidase. Kinetic results have shown that this compound is a mixed-type inhibitor with higher affinity to the free enzyme than to the enzyme-substrate complex. The results of the molecular docking and molecular dynamics show that the carboxylic group of the inhibitor can form a salt bridge with Arg880 and a hydrogen bond with Thr1010. These interactions can be key factors in the enzyme-inhibitor complex stabilization.4-(Фуран-2-іл)бензойні кислоти з фрагментом піразолону було синтезовано та досліджено як інгібітори ксантиноксидази. Цей ензим є однією з терапевтичних мішеней для лікування гіперурикемії та супутніх захворювань. Вивчені сполуки демонстрували низькомікромолярні значення IC50 щодо ензиму in vitro, залежно від замісників у положенні 3 піразолонового кільця. Однак спостережувані інгібувальні ефекти знижувались за наявності бичачого сироваткового альбуміну або твіну-80. Серед синтезованих похідних піразолону 4-(5-((3-метил-5-оксо-1-феніл-1,5-дигідро-4H-піразол-4-іліден)метил)фуран-2-іл)бензойна кислота виявилась найпотужнішим інгібітором ксантиноксидази. Кінетичні дослідження засвідчили, що ця сполука є інгібітором змішаного типу з більшою спорідненістю до вільного ензиму, ніж до ензим-субстратного комплексу. Результати молекулярного докінгу і молекулярної динаміки свідчать про те, що карбоксильна група інгібітора може формувати сольовий місток із залишком Arg880 і водневий зв’язок із залишком Thr1010. Ці взаємодії можуть бути ключовими факторами стабілізації комплексу ензим-інгібітор

In silico study of 4-phosphorylated derivatives of 1,3-oxazole as inhibitors of Candida albicans fructose-1,6-bisphosphate aldolase II

In this study, the synthesis, in vitro anti-Candida activity and molecular modeling of 4-phosphorylated derivatives of 1,3-oxazole as inhibitors of Candida albicans fructose-1,6-bisphosphate aldolase (FBA-II) are demonstrated and discussed. Significant similarity of the primary and secondary structure, binding sites and active sites of FBA-II C. albicans and Mycobacterium tuberculosis are established. FBA-II C. albicans inhibitors contained 1,3-oxazole-4-phosphonates moiety are created by analogy to inhibitors FBA-II M. tuberculosis. The experimental studies of the anti-Candida activity of the designed and synthesized compounds have shown their high activity against standard strain and its C. albicans fluconazole resistant clinical isolate. It was hypothesized that the growth suppression of fluconazole-resistant С. albicans strain may be due to the inhibition of aldolase fructose-1,6-bisphosphate. A qualitative homology 3D model of the C. albicans FBA-II was created using SWISS-MODEL server. The probable mechanism of FBA-II inhibition by studied 4-phosphorylated derivatives was shown using molecular docking. The main role of amino acid residues His110, His226, Gly227, Leu248, Val238, Asp144, Lys230, Glu147, Gly227, Ala112, Leu145 and catalytic zinc atom in the formation of stable ligand-protein complexes with ΔG = –6.89, –7.2, –7.16, –7.5, –8.0, –7.9 kcal/mol was shown.Thus, the positive results obtained in the work were demonstrated the promise of using the proposed homology 3D model of the C. albicans FBA-II as the target for the search and development of new anti-Candida agents against azole-resistant fungal pathogens. Designed and studied 4-phosphorylated derivatives of 1,3-oxazole having a direct inhibiting FBA-II molecular mechanism of action can be used as perspective drug-candidates against resistant C. albicans strains