Designing Cobalt(II) Complex for Chemoselective Synthesis of 2-Aryl-3-Formyl Indoles from Amino Alcohols and Alcohols†.

An air-stable, inexpensive, and isolable cobalt(II) complex (C1) of N-((1-methyl-1H-imidazol-2-yl)methyl)-2-(phenylselanyl)ethan amine (L1) was synthesized and characterized. The complex was used to catalyze a one-pot cascade reaction between 2-(2-aminophenyl)ethanols and benzyl alcohol derivatives. Interestingly, 2-aryl-3-formylindole derivatives were formed instead of N-alkylated or C-3 alkylated indoles. A broad substrate scope can be activated using this protocol with only 5.0 mol % catalyst loading to achieve up to 87 % yield of 2-aryl-3-formylindole derivatives. The mechanistic studies suggested that the reaction proceeds through tandem imine formation followed by cyclization.

Mercaptopurine induced myelosuppression in a child with a NUDT15 rs116855232 homozygous variant.

INTRODUCTION: Mercaptopurine (6-MP) is the backbone of the consolidation and maintenance therapy for paediatric acute lymphoblastic leukaemia (ALL). Nevertheless, it can cause critical myelosuppression. Predicting adverse reactions to 6-MP often involves the investigation of pharmacogenetic variants; in particular thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15). Lately, NUDT15 variants have been shown to play a significant pharmacogenetic role in predicting 6-MP intolerance in children of Asian descent. CASE REPORT: We present a six-year-old male child of Indian origin with persistent cytopenia after treatment. This prompted targeted sequencing of the genes TPMT and NUD15. The results revealed two copies of the variant of NUD15 rs116855232, that is, NUDT15*2 genotype. MANAGEMENT AND OUTCOME: Since the NUDT15*2 allele classified the patient as a poor metabolizer, he was restarted on a low dose of 6-MP, which he tolerated. DISCUSSION: Individuals with the NUDT15*2allele (*2/*2 genotype) are poor metabolizers of thiopurines which results in an adverse reaction to 6-MP. About 3.5% of Indians show variations in the TPMT gene as compared to 19.4% variations observed in NUDT15, which makes the latter a more reliable disease marker.

Hypertrophic post-acne scarring is associated with a single nucleotide polymorphism (rs243865) in the matrix metalloproteinase-2 gene.

BACKGROUND AND OBJECTIVE: Aberrant tissue expression of matrix metalloproteinases has been observed in acne. Our objective was to study the relevance of MMP-2 (-1306 C/T, rs243865) and TIMP-2 (-418 G/C, rs8179090) single nucleotide polymorphisms (SNP) in acne and post-acne scarring. PATIENTS AND METHODS: 512 patients (169 having acne without scarring, 319 having atrophic acne scarring, 24 having hypertrophic acne scarring) and 161 age-matched controls were recruited from the Dermatology Outpatient Department after obtaining informed written consent. Venous blood (5 ml) was collected for genotyping by Polymerase Chain Reaction (PCR)-Restriction Fragment Length Polymorphism (RFLP) method. The severity of acne and acne-scarring were graded. RESULTS: Males had a significantly increased risk of developing severe acne (P = 0.012), extra-facial acne (P = 0.047) and extra-facial acne scarring (P = 0.0001). The presence of inflammatory acne positively correlated with severity of scarring (P = 0.001). Subjects with a homozygous CC genotype of MMP-2 (-1306 C/T) had 1.0, 7.8 and 8.2 times the odds of developing hypertrophic scarring when compared to controls (P = 0.05, 95 % CI: 0.7-1.6), subjects having acne without scarring (P = 0.047, 95 % CI: 1.0-59.9) and subjects having atrophic scarring, respectively (P = 0.041, 95 % CI: 1.1-59.9). CONCLUSIONS: A significant association was observed between hypertrophic post-acne scarring and the CC genotype of MMP-2 (-1306 C/T).

Assoziation hypertropher Post-Akne-Narben mit Einzelnukleotid-Polymorphismus (rs243865) im Matrix-Metalloproteinase-2-Gen.

HINTERGRUND UND ZIEL: Bei Akne wurde eine abweichende Gewebeexpression von Matrix-Metalloproteinasen beobachtet. Ziel unserer Studie war es, die Bedeutung von Polymorphismen einzelner Nukleotide (single nucleotide polymorphisms, SNPs) in MMP-2 (-1306 C/T, rs243865) und TIMP-2 (-418 G/C, rs8179090) bei Akne und Post-Akne-Narben zu untersuchen. PATIENTEN UND METHODEN: 512 Patienten (169 mit Akne ohne Narbenbildung, 319 mit atrophen Aknenarben, 24 mit hypertrophen Aknenarben) und 161 gleichaltrige Kontrollen wurden nach Erhalt der schriftlichen Einwilligungserklärung aus der Ambulanz der Hautklinik in die Studie aufgenommen. Zur Genotypisierung mittels Polymerasekettenreaktion-Restriktionsfragmentlängenpolymorphismus (PCR-RFLP) wurde venöses Blut (5 ml) entnommen. Der Schweregrad von Akne und Akne-bedingter Narbenbildung wurde bestimmt. ERGEBNISSE: Männer hatten ein deutlich erhöhtes Risiko schwere Akne (p = 0,012), Akne außerhalb des Gesichts (p = 0,047) und Aknenarben außerhalb des Gesichts (p = 0,0001) zu entwickeln. Entzündliche Akne korrelierte positiv mit dem Schweregrad der Narbenbildung (p = 0,001). Die Wahrscheinlichkeit für die Bildung hypertropher Narben war bei Personen mit homozygotem CC-Genotyp von MMP-2 (-1306 C/T) gegenüber Kontrollen nicht verändert (Faktor 1,0; p = 0,05; 95 %-KI: 0,7-1,6), jedoch gegenüber Personen mit Akne ohne Narbenbildung um den Faktor 7,8 (p = 0,047; 95 %-KI: 1,0-59,9) und gegenüber Personen mit atrophen Narben um den Faktor 8,2 (p = 0,041; 95 %-KI: 1,1-59,9) erhöht. SCHLUSSFOLGERUNGEN: Es wurde eine signifikante Assoziation zwischen der Bildung hypertropher Post-Akne-Narben und dem CC-Genotyp von MMP-2 (-1306 C/T) beobachtet.