Microwave-assisted modified synthesis of C8-analogues of naturally occurring methylxanthines: Synthesis, biological evaluation and their practical applications.

An efficient, microwave-assisted, oxidant-interceded, transition-metal-free, cross-dehydrogenative Csp2-Csp3 coupling of C8-Caffeine 2/Theobromine 3/theophylline 4 with substituted aliphatic alcohols 11a-lvia CH bond activation for the preparation of series of substituted C8-(hydroxymethyl) Caffeine 12a-l/theobromine 13a-c/theophylline 14a-b has been developed using microwave irradiation upto 98% yield. The reaction proceeds smoothly in the presence of tert-butyl hydroperoxide (TBHP) under solvolysis condition at 120 °C for 20 min to corresponding substituted C8-(hydroxymethyl)-methylxanthine derivatives in good to excellent yields. The good substrate scope, control experiments, gram-scale synthesis, and practical synthetic transformations further highlights the practicality of this methodology. These C8-(hydroxymethyl) Caffeine 12a-l, 13a-c and 14a-b have been found to show promising in vitro antioxidant as well as antiplatelet activities.

Artemisinin-derived antimalarial endoperoxides from bench-side to bed-side: Chronological advancements and future challenges.

According to WHO World Malaria Report (2018), nearly 219 million new cases of malaria occurred and a total no. of 435 000 people died in 2017 due to this infectious disease. This is due to the rapid spread of parasite-resistant strains. Artemisinin (ART), a sesquiterpene lactone endoperoxide isolated from traditional Chinese herb Artemisia annua, has been recognized as a novel class of antimalarial drugs. The 2015 "Nobel Prize in Physiology or Medicine" was given to Prof Dr Tu Youyou for the discovery of ART. Hence, ART is termed as "Nobel medicine." The present review article accommodates insights from the chronological advancements and direct statistics witnessed during the past 48 years (1971-2019) in the medicinal chemistry of ART-derived antimalarial endoperoxides, and their clinical utility in malaria chemotherapy and drug discovery.

An efficient synthesis and biological evaluation of novel analogues of natural product Cephalandole A: A new class of antimicrobial and antiplatelet agents.

Cephalandole A 2, a small indole alkaloid isolated from the Taiwanese orchid Cephalanceropsis gracilis (Orchidaceae), exhibits anticancer activity. Surprisingly, this natural product has not been evaluated for any other biological activity so far. To discover other novel potential of Cephalandole A 2, an efficient and economic synthetic protocol for novel Cephalandole A analogues 21a-o has been developed, in only 3 steps from using indole, and applied for their biological activity. Biological testing showed that Cephalandole A 2 and its novel analogues 21a-o exhibited potential antimicrobial and antiplatelet activity in preliminary assay. To the best of our knowledge, this is the first report of Cephalandole A 2 and its novel synthetic analogues 21a-o as a new class of antimicrobial and antiplatelet agents. In this study, 2 and other analogues i.e., 21b, 21d, 21i and 21o showed promising antimicrobial activity against the phytopathogenic bacteria and fungi. Cephalandole A 2, 21c, 21f and 21i, also showed potent antiplatelet activity.

Vitamin D supplementation reduces thyroid peroxidase antibody levels in patients with autoimmune thyroid disease: An open-labeled randomized controlled trial.

BACKGROUND AND AIMS: Although Vitamin D deficiency has been linked to autoimmune thyroid disorders (AITD), the impact of Vitamin D supplementation on thyroid autoimmunity is not known. This study aimed to evaluate the impact of Vitamin D supplementation on thyroid autoimmunity (thyroid peroxidase antibody [TPO-Ab] titers) in patients with newly diagnosed AITD in a randomized controlled trial. MATERIALS AND METHODS: One hundred two patients with newly diagnosed AITD (TPO-Ab > 34 kIU/L and/or sonographic evidence of thyroiditis) patients were randomized into Group-1 (intervention group) and Group-2 (control group). Group-1 received cholecalciferol 60,000 IU weekly and calcium 500 mg/day for 8 weeks; Group-2 received calcium 500 mg/day for 8 weeks. Responders were defined as ≥25% fall in TPO-Ab titers. Individuals with at least 3-month follow-up were analyzed. Trial is registered at ctri.nic.in (CTRI/2015/04/005713). RESULTS: Data from 100 AITD patients (68 with thyroid stimulating hormone [TSH] ≤10 mIU/L, 32 with TSH > 10 mIU/L), 93% having Vitamin D insufficiency, were analyzed. TPO-Ab titers were highest among patients in the lowest 25-hydroxyvitamin D quartile (P = 0.084). At 3 months follow-up, there was significant fall in TPO-Ab in Group-1 (-46.73%) as compared to Group-2 (-16.6%) (P = 0.028). Sixty-eight percentage patients in Group-1 were responders compared to 44% in Group-2 (P = 0.015). Kaplan-Meier analysis revealed significantly higher response rate in Group-1 (P = 0.012). Significantly greater reduction in TPO-Ab titers was observed in AITD with TSH ≤ 10 mIU/L compared to TSH > 10 mIU/L. Cox regression revealed Group-1 followed by TPO-Ab and free tetraiodothyronine levels to be a good predictor of response to therapy (P = 0.042, 0.069, and 0.074, respectively). CONCLUSION: Vitamin D supplementation in AITD may have a beneficial effect on autoimmunity as evidence by significant reductions in TPO-Ab titers.

Prevalence and severity of vitamin D deficiency in patients with diabetic foot infection.

The aim of the present research was to study the prevalence and severity of vitamin D deficiency in patients with diabetic foot infection. Patients were enrolled in two groups: diabetic patients with foot infection (n 125) as cases and diabetic patients without the infection as controls (n 164). Serum 25-hydroxyvitamin D (25(OH)D) was measured by RIA. Data were presented as means and standard deviations unless otherwise indicated and were analysed by SPSS. Results revealed that 25(OH)D (nmol/l) was significantly lower (40·25 (sd 38·35) v. 50·75 (sd 33·00); P < 0·001) in cases than in controls. Vitamin D inadequacy (25(OH)D < 75 nmol/l) was equally common in cases and controls (OR 1·45, 95 % CI 0·8, 3·0; P = 0·32), but cases had a greater risk of vitamin D deficiency (25(OH)D < 50 nmol/l) than controls (OR 1·8, 95 % CI 1·1, 3·0; P = 0·02). Risk of severe vitamin D deficiency (25(OH)D < 25 nmol/l) was significantly higher in cases than in controls (OR 4·0, 95 % CI 2·4, 6·9; P < 0·0001). Age, duration of diabetes and HbA1c were significantly higher in cases than in controls and therefore adjusted to nullify the effect of these variables, if any, on study outcome. The study concluded that vitamin D deficiency was more prevalent and severe in patients with diabetic foot infection. This study opens up the issue of recognising severe vitamin D deficiency (< 25 nmol/l) as a possible risk factor for diabetic foot infections and the need for vitamin D supplementation in such patients for a better clinical outcome. This could be substantiated by similar data from future studies.

New Drimane Sesquiterpenoids from Tidestromia oblongifolia.

From an acetone extract of the aerial parts of Tidestromia oblongifolia (Amaranthaceae), a new drimane sesquiterpenoid bearing an 11,12,13-trihydroxydrimene skeleton (1) as well as the 11,12 acetonide of 1 were isolated. Three known stigmastane triterpenoids were also isolated. Structures were elucidated with the aid of 1D and 2D NMR spectroscopic techniques. The absolute configuration of 1 was confirmed by single-crystal x-ray crystallography. This is the first report on phytochemical constituents from any plant of the genus Tidestromia and is the first report of the occurrence of drimanes in the Amaranthaceae.