Abstract
Podophyllotoxin, along with its various derivatives and congeners are widely recognized as broad-spectrum pharmacologically active compounds. Etoposide, for instance, is the frontline chemotherapeutic drug used against various cancers due to its superior anticancer activity. It has recently been redeveloped for the purpose of treating cytokine storm in COVID-19 patients. Podophyllotoxin and its naturally occurring congeners have low bioavailability and almost all these initially discovered compounds cause systemic toxicity and development of drug resistance. Moreover, the production of synthetic derivatives that could suffice for the clinical limitations of these naturally occurring compounds is not economically feasible. These challenges demanded continuous devotions towards improving the druggability of these drugs and continue to seek structure-optimization strategies. The discovery of renewable sources including microbial origin for podophyllotoxin is another possible approach. This review focuses on the exigency of innovation and research required in the global R&D and pharmaceutical industry for podophyllotoxin and related compounds based on recent scientific findings and market predictions.
Highlights
Podophyllotoxin is an aryltetralin-type lignan isolated from species of Podophyllum [1,2]
Two most common sources are the rhizomes of Podophyllum peltatum (American mayapple) and Sinopodophyllum hexandrum Royle (Barberry family) [1,3]
The main fungal sources used for industrial podophyllotoxin production are; Trametes hirsuta [110], Fusarium oxysporum [111], Fungus Alternaria [112], Mucor fragilis [113], Fusarium solani [114], Trametes histuria [110], Sebacina vermifera, Phialocephala fortinii [115]
Summary
Podophyllotoxin is an aryltetralin-type lignan isolated from species of Podophyllum [1,2]. The clinical practicality of podophyllotoxin was, largely tampered because of its undesirable secondary effects such as gastrointestinal toxicity, neurotoxicity, hair-loss, and bone marrow suppression, etc., which led to the finding of less-toxic derivatives or analogues These molecules have since become a structural base for the development of new therapeutic agents. The therapeutic use of these drugs is hindered by myelosuppression, development of drug-resistance and their cytotoxic activity towards normal body cells This review is aimed at providing an insight to podophyllotoxin research and helps delineate further investigations, which are needed in this field
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