Methyl 9-(1-methyl-1H-indol-3-yl)-9-oxononanoate

Methyl 9-(1-methyl-1H-indol-3-yl)-9-oxononanoate was synthesized using Friedel-Crafts acylation between N-methyl indole and methyl 9-chloro-9-oxononanoate. The structure of the newly synthesized compound was elucidated using H-1-NMR, C-13-NMR, NOESY-1D, ESI-MS, FT-IR, and UV-Vis spectroscopy

An Easy Route to Enantiomerically Enriched 7- and 8-Hydroxystearic Acids by Olefin Metathesis - Based Approach

The synthesis of enantiomerically enriched 7- and 8-hydroxystearic acids (7- and 8-HSA) has been successfully accomplished starting from chiral non racemic 1-pentadecen-4-ol and 1-tetradecen-4-ol respectively. Their Yamaguchi\u2019s esterification with 4-pentenoic and 5-hexenoic acids respectively afforded the suitable dienic esters which were submitted to ring closing metathesis reaction. After hydrogenation and basic hydrolysis of the complex reaction mixture, chiral non racemic 7- and 8-HSA were obtained in about 40% total yield

Vibrational Raman and IR data on brown hair subjected to bleaching

Brown human hair was bleached three times (45 min × 3) and four times (45 min × 3 + 15 min) with commercial formulations containing persulfate salts and hydrogen peroxide. The hair samples were characterized by Raman and IR spectroscopy in the Attenuated Total Reflectance (ATR) mode to gain more insights into the possible secondary structure and Cα-Cβ-S-S-Cβ-Cα conformational changes induced by bleaching. The latter were evaluated through band-fitting procedures; the relative content of the disulfide bridges and oxidized sulfur species (cysteic acid, Bunte salt, cystine oxides) was assessed. The observed conformational changes could be significant in developing restoring agents to be used after hair decoloration. The use of two different spectroscopic techniques allowed to discriminate the information coming from the cortical region of hair (Raman) and the cuticle (ATR/IR). This article refers to “Structural investigation on damaged hair keratin treated with α,β-unsaturated Michael acceptors used as repairing agents” (Di Foggia et al., Int. J. Biol. Macromol. 167 (2021) 620–632 https://doi.org/10.1016/j.ijbiomac.2020.11.194)

Ruthenium-thymine acetate binding modes: Experimental and theoretical studies

Ruthenium complexes have proved to exhibit antineoplastic activity, related to the interaction of the metal ion with DNA. In this context, synthetic and theoretical studies on ruthenium binding modes of thymine acetate (THAc) have been focused to shed light on the structure-activity relationship. This report deals with the reaction between dihydride ruthenium mer-[Ru(H)2(CO)(PPh3)3], 1 and the thymine acetic acid (THAcOH) selected as model for nucleobase derivatives. The reaction in refluxing toluene between 1 and THAcOH excess, by H2 release affords the double coordinating species k1-(O)THAc-, k2-(O,O)THAc-[Ru(CO)(PPh3)2], 2. The X-ray crystal structure confirms a simultaneous monohapto, dihapto- THAc coordination in a reciprocal facial disposition. Stepwise additions of THAcOH allowed to intercept the monohapto mer-k1(O)THAc-Ru(CO)H(PPh3)3] 3 and dihapto trans(P,P)-k2(O,O)THAc-[Ru(CO)H(PPh3)2] 4 species. Nuclear magnetic resonance (NMR) studies, associated with DFT (Density Function Theory)-calculations energies and analogous reactions with acetic acid, supported the proposed reaction path. As evidenced by the crystal supramolecular hydrogen-binding packing and 1H NMR spectra, metal coordination seems to play a pivotal role in stabilizing the minor [(N=C(OH)] lactim tautomers, which may promote mismatching to DNA nucleobase pairs as a clue for its anticancer activity

Susceptibility of Cryptococcus neoformans and Cryptococcus gattii from clinical and environment sources in Nairobi, Kenya

Objective: To determine anti-fungal susceptibility of Cryptococcus neoformans andCryptococcus gattii from environmental and clinical sources in Nairobi, Kenya.Design: Prospective study.Setting: Kenya Medical Research Institute, Mycology laboratory, Nairobi, Kenya.Subjects: A total of 123 isolates were tested for their susceptibility to fluconazole(FLC), amphotericin B(AMP) and fluorocytosine (5FC). Clinical isolates were 70(66Cryptococcus neoformans and 4 Cryptococcus gattii) while environmental isolates were53(41 C. neoformans and 12 C. gattii). The isolates were characterised using variousphenotypic tests including microscopic morphology, physiological and biochemicaltests (API 20 Caux), pigmentation on bird seed agar and reaction on canavanineglycine-bromthymolblue agar. European Committee on Anti-microbial SusceptibilityStandards (EUCAST) was used as the reference method for susceptibility testing.Results: Most C. neoformans isolates; clinical (61/66; 92.4%) and environmental (38/41;92.7%) were susceptible to FLC. The number of C. neoformans isolates inhibited atsusceptible dose dependent (SDD) range (16-32μg/ml) by FLC were clinical (4/66; 6.1%)and environmental (2/41; 4.9%). One C. neoformans isolate each; clinical (1/66; 1.5%)and environmental (1/41; 2.4%) was resistant to FLC. All C. gatti isolates from clinicaland environmental were fully susceptible to FLC. The percentage of C. neoformansisolates that were susceptible (S) (MIC ≤ 1.0 μg/ml) to AMP were; clinical(52/66; 90.2%)and environmental (37/41; 78.8%) while the rest were susceptible dose dependent(SDD) with MIC (2-8μg/ml). Reduced susceptibilities to 5FC was displayed in allclinical and environmental C. neoformans and C. gatii isolates; for instance resistanceto 5FC was reported in C. neoformans; clinical (8/66; 12.1%) and environmental (1/41;2.4 %). Among the C. gattii isolates there was also decreased susceptibility to 5FCwith Minimum Inhibition Concentration (MIC) range of between 0.5-32 μg/ml. Therewere no significant differences in susceptibility ranges among all the clinical andenvironmental isolates.Conclusion: This study demonstrated reduced susceptibilities among C. neoformansand C. gattii isolates to commonly used anti-fungal drugs

Reinvestigation of the tautomerism of some substituted 2-hydroxypyridines

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Synthesis of novel structural hybrids between aza-heterocycles and azelaic acid moiety with a specific activity on osteosarcoma cells

Nine compounds bearing pyridinyl (or piperidinyl, benzimidazolyl, benzotriazolyl) groups bound to an azelayl moiety through an amide bond were synthesized. The structural analogy with some histone deacetylase inhibitors inspired their syntheses, seeking new selective histone deacetylase inhibitors (HDACi). The azelayl moiety recalls part of 9-hydroxystearic acid, a cellular lipid showing antiproliferative activity toward cancer cells with HDAC as a molecular target. Azelayl derivatives bound to a benzothiazolyl moiety further proved to be active as HDACi. The novel compounds were tested on a panel of both normal and tumor cell lines. Non-specific induction of cytotoxicity was observed in the normal cell line, while three of them induced a biological effect only on the osteosarcoma (U2OS) cell line. One of them induced a change in nuclear shape and size. Cell-cycle alterations are associated with post-transcriptional modification of both H2/H3 and H4 histones. In line with recent studies, revealing unexpected HDAC7 function in osteoclasts, molecular docking studies on the active molecules predicted their proneness to interact with HDAC7. By reducing side effects associated with the action of the first-generation inhibitors, the herein reported compounds, thus, sound promising as selective HDACi

Synthesis and Antiproliferative Insights of Lipophilic Ru(II)-Hydroxy Stearic Acid Hybrid Species

Metallodrugs represent a combination of multifunctionalities that are present concomitantly and can act differently on diverse biotargets. Their efficacy is often related to the lipophilic features exhibited both by long carbo-chains and the phosphine ligands. Three Ru(II) complexes containing hydroxy stearic acids (HSAs) were successfully synthesized in order to evaluate possible synergistic effects between the known antitumor activity of HSA bio-ligands and the metal center. HSAs were reacted with [Ru(H)2CO(PPh3)3] selectively affording O,O-carboxy bidentate complexes. The organometallic species were fully characterized spectroscopically using ESI-MS, IR, UV-Vis, and NMR techniques. The structure of the compound Ru-12-HSA was also determined using single crystal X-ray diffraction. The biological potency of ruthenium complexes (Ru-7-HSA, Ru-9-HSA, and Ru-12-HSA) was studied on human primary cell lines (HT29, HeLa, and IGROV1). To obtain detailed information about anticancer properties, tests for cytotoxicity, cell proliferation, and DNA damage were performed. The results demonstrate that the new ruthenium complexes, Ru-7-HSA and Ru-9-HSA, possess biological activity. Furthermore, we observed that the Ru-9-HSA complex shows increased antitumor activity on colon cancer cells, HT29

How does a biopsy of endoscopically normal terminal ileum contribute to the diagnosis? Which patients should undergo biopsy?

Background: Terminal ileum endoscopy and biopsy are the diagnostic tools of diseases attacking the ileum. However, abnormal histological findings can be found in endoscopically normal terminal ileum.Objective: This study was performed to evaluate the histopathological results of biopsies from endoscopically normal terminal ileum in order to determine pre-procedure clinical and laboratory factors predicting abnormal histopathological results, if any.Methods: A total of 297 patients who underwent colonoscopy and terminal ileum biopsy and had normal terminal ileum or a few aphthous ulcers in the terminal ileum together with completely normal colon mucosa were included in the study. The patients were grouped into two arms as normal cases and cases with aphthous ulcers. Histopathological and pre-procedural laboratory results of patients were analyzed according to their indications.Results: The terminal ileum was endoscopically normal in 200 patients, and 97 patients had aphthous ulcers. Chronic ileitis rate was present in 5.5% of those with endoscopically normal terminal ileum and in 39.2% of the patients with aphthous ulcers. In both groups, the highest rate of chronic ileitis was detected in the patients with known inflammatory bowel disease (IBD) (15.4 and 50%, respectively), anemia (9.5 and 43.5%, respectively), and in the patients having chronic diarrhea together with abdominal pain (7.7 and 44.8%, respectively). We found that the sensitivity of mean platelet volume for predicting chronic ileitis was 87% and the specificity was 45% at a cut-off value lower than 9.35 fl.Conclusion: In anemia indication or chronic diarrhea together with abdominal pain, the frequency of aphthous ulcers detected by ileoscopy and the frequency of chronic ileitis detected histopathologically despite a normal-appearing ileum were elevated.Keywords: Terminal ileum; ileoscopy; chronic ileitis; inflammatory bowel diseas