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Saccharonol B,a new cytotoxic methylated isocoumarin from Saccharomonospora azurea
Authors:Baljinder Singh  Rajinder Parshad  R.K. Khajuria  Santosh K. Guru  Anup S. Pathania  Rashmi Sharma  Reena Chib  Subrayashastry Aravinda  Vivek K. Gupta  Inshad A. Khan  Shashi Bhushan  Sandip B. Bharate  Ram A. Vishwakarma
Affiliation:1. Natural Products Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India;2. Academy of Scientific & Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India;3. Fermentation Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India;4. Cancer Pharmacology Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India;5. Clinical Microbiology Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India;6. Medicinal Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India;g X-ray Crystallography Laboratory, Post-Graduate Department of Physics & Electronics, University of Jammu, Jammu 180001, India
Abstract:From an antimicrobial gram-positive actinomycete strain of Saccharomonospora azurea (MTCC11714) isolated from high altitude soil of Kargil (J&K, India), a new isocoumarin saccharonol B (2) along with two known compounds viz. saccharonol A (1) and piericidin A3 (3) was isolated and characterized. The structure of the new compound was established based on extensive 2D-NMR data. Saccharonol B (2) exhibited mild antimicrobial activity against a standard panel of microorganisms Staphylococcus aureus ATCC 29213, Candida albicans ATCC 90028, and Aspergillus fumigatus MTCC 1811 with MIC values in the range of 128–248 μg/mL. Saccharonol B (2) and piericidin A3 (3) showed selective cytotoxic activity against human pancreatic carcinoma cell line (MIAPaCa-2) with IC50 values of 9 and 8 μM, respectively. Mechanistic studies indicated that saccharonol B (2) arrests S-phase of the cell cycle and causes dose-dependent loss of mitochondrial potential in MIAPaCa-2 cells.
Keywords:Saccharonol B   Saccharomonospora azurea   Cytotoxic   Actinomycete   Antimicrobial   Isocoumarin
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