Caerulomycin A—An Antifungal Compound Isolated from Marine Actinomycetes

Actinomycetes have been prolific sources of novel secondary metabolites with a range of biological activities that may ultimately find application as therapeutic compounds. Hence several drug discovery companies are engaged in isolation of novel bioactive metabolites from these microbial sources. Antibiotics form the major class of such bioactive metabolites and have been widely used for treating infectious diseases. One of the most critical problems in clinical practice is the increase of prevalence of drug resistant strains, especially azole resistance among fungi. Due to this, there is a constant need for development of new antifungal antibiotics having novel scaffolds and/or mechanism of action. In our in-house screening program in the quest of novel and superior antifungal compounds, an actinomycetes strain PM0525875 was isolated from a marine invertebrate. The extracts of this microbe showed potent in-vitro antifungal activity against drug resistant fungal strains. The antifungal active peak from the extract obtained by shake flask fermentation was identified by chromatographic and other analytical techniques during bioactivity guided isolation. Later the fermentation conditions were optimized in 30 L fermentor for the production of sufficient amount antifungal compound for complete structural characterization. Consequently the fermented broth extract was subjected to bioactivity-guided fractionation, to isolate the active principle using different preparative chromatographic techniques followed by its characterization. The active principle was characterized to be Caerulomycin A. Minimum inhibitory concentration (MIC) of the compound was found in the range of 0.39 - 1.56 μg/ml against pathogenic fungal test strains. The phylogenetic analysis of producer strain using 16S rRNA sequence showed closest match with Actinoalloateichus cyanogriseus. Herewith we report the isolation of Caerulomycin A from marine invertebrate-associated Actinoalloteichus sp. using optimized medium and fermentation conditions.

Efficacy and Safety of PDM011011 Capsules as Compared to Metformin in Subjects with Type-2 Diabetes Mellitus: An Open-Label, Randomized, Active-Controlled, Multicentric, Phase III Study

Context: Bitter melon (Momoradica charantia) is one of the well-known plants used for lowering blood glucose since antiquity. Aims: To compare the efficacy and safety of PDM011011 capsule (1200 mg/day) with Metformin (1000 mg/day) in a 15 weeks study using mean change in fasting plasma glucose (FPG) and Hb1Ac% in subjects with type 2 diabetes mellitus (T2DM). Settings and Design: This is an open-label, randomized, active-controlled, multicentric, phase III study. Methods and Material: A total of 123 eligible patients were randomized in 2:1 ratio in PDM011011 and Metformin arm. Total 83 subjects received PDM011011 capsule (1200 mg/day) and 40 subjects received Metformin (1000 mg/day) in their respective arms for 15 weeks. Subjects were analyzed for FPG and Hb1Ac% at baseline and during treatment visits (Visit 3 to Visit 7). Safety assessments were carried out. Results: In this study, the significant reduction in mean FPG level was observed after treatment with PDM011011 capsule and Metformin in T2DM patients. The mean change from baseline to week 15 in FPG was 14.52 mg/dL (95% CI: 6.36, 22.67) in the PDM011011-treated subjects and 28.34 mg/dL (95% CI: 21.35, 35.32) in the Metformin-treated subjects. At week 15, the mean change from baseline in HbA1c levels was 0.27% (95% CI: 0.06, 0.47) in the PDM011011 arm and 0.62% (95% CI: 0.40, 0.83) in the Metformin arm. Conclusion: PDM011011 capsule (1200 mg/day) exhibited the modest efficacy and safety as compared to Metformin (1000 mg/day) in type 2 diabetes patients.

Efficacy and Safety of Tinefcon® Tablets in Subjects with Plaque Psoriasis: An Open Label, Non-Comparative, Multicenter, Phase IV Trial

Importance: This post-marketing surveillance study was conducted to evaluate real-world information about the efficacy and safety of oral Tinefcon? tablets (Sphaeranthus indicus based) in plaque psoriasis patients. Materials and Methods: Patients aged at least 18 years and older with clinical diagnosis of plaque psoriasis, were enrolled in this open label, non-comparative, multicenter trial. All eligible subjects received four 700 mg Tinefcon? tablets/day for 12 weeks. The primary outcome measure was percent change in Psoriasis Area Severity Index (PASI) score from baseline to week 12. The secondary outcome measures were Physician Global Assessment (PGA), Nail Psoriasis Severity Index (NAPSI), Psoriatic Arthritis Evaluation and Gene Expression Profiling and Immunohistochemistry. Results: After completion of Tinefcon? treatment at 12 weeks, more than half of subjects (52%) achieved PASI 50 response;PASI 75 response was attained in 68 (23%) subjects and PASI 90 response in 22 (7%) subjects. Five subjects with severe psoriasis achieved PASI 90 without receiving any concomitant medication. Reduction in severity as assessed by PGA was observed in more than half of patients with moderate disease. Histopathological evaluation revealed that epidermal thickness was considerably reduced in 66% of subjects. The expression of inflammatory marker S100A9 protein was(meaningfully reduced in 60% patients with non-significant reduction of Keratin 10 protein expression. Gene expression analysis showed increase down regulation of SERPINB4;PI3 and KRT16 genes after a 12-week treatment period in subjects with higher PASI scores. Conclusion: Oral Tinefcon? tablets showed good efficacy and had a favorable safety profile in plaque psoriasis patients.