ABSTRACT
Withania somnifera is one of the highly reputed medicinal plants of India. Its steroidal constituents exist in the form of two major substitution patterns, viz. withaferin A (1) and withanone (5). Withaferin A with oxidation at carbons 4, 5, and 6 is considered as an active type, especially as anticancer, whereas the withanones with oxidation at carbons 5, 6, and 7 rarely show any activity. We prepared a series of derivatives with modifications at carbons 5, 6, and 7 in ring B of these withanolides to study the role of the epoxide group towards the cytotoxic property of these bioactive steroids. We have converted withanolides into the respective thiiranes, amino alcohols and alcohols by selective reactions at the epoxide ring and were evaluated for in vitro anticancer activity against four cancer cell lines to study the structure activity relationships. The transformations of the epoxide group in withanolides of the withaferin A type showed moderate reduction in their cytotoxicity whereas the almost inactive withanones have shown some improvements in their alcohol derivatives.
Subject(s)
Antineoplastic Agents/pharmacology , Triterpenes/pharmacology , Withania/chemistry , Withanolides/pharmacology , Antineoplastic Agents/chemistry , Caco-2 Cells , Cell Line, Tumor , Cell Survival/drug effects , Humans , Inhibitory Concentration 50 , MCF-7 Cells , Molecular Structure , Plant Leaves/chemistry , Plants, Medicinal/chemistry , Structure-Activity Relationship , Triterpenes/chemistry , Withanolides/chemistryABSTRACT
Lupus-like glomerulnephritis in patients with negative lupus serologies and no extra-renal manifestations of lupus can create a diagnostic dilemma. We describe a 53-year-old gentleman with chronic hepatitis C virus (HCV) infection who presented with dialysis-requiring renal failure, renal histologic findings of "full-house" immunofluorescence label and tubuloreticular inclusions on electronic microscopy, but no extra-renal or laboratory signs of systemic lupus erythematosis. Attempted treatment with cyclophosphamide and corticosteroids was limited by cyclophosphamide hypersensitivity. The patient remained dialysis-dependent over 18 months of observation and did not develop extra-renal clinical or biological manifestations of lupus. Mimics of seronegative lupus with isolated renal involvement can include HCV-related autoimmunity. Treatment of acute glomerulonephritis may be similar initially, but other concerns in patients with HCV infection include excluding cryoglobulinemia, the potential impact of immunosuppression therapy on liver disease and consideration of subsequent use of antiviral therapy. Given the increasing prevalence of HCV globally, the recognition of extra-hepatic autoimmune manifestations of HCV infection will likely increase.
ABSTRACT
An unusual case of posterior scleritis mimicking macular serpiginous choroiditis is reported.
