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Cytochrome P450 Enzymes for the Synthesis of Novel and Known Drugs and Drug Metabolites
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Sanjana Haque, Yuqing Gong, Sunitha Kodidela, Mohammad A. Rahman, Sabina Ranjit, Santosh Kumar
Targeting CYP51, a sterol demethylase isolated from fungi, is a well-known biosynthetic pathway to synthesize sterol drug candidates (Zhu et al., 2006). Antifungal agents like azoles, anti-tuberculosis drugs, drugs against Chagas disease, triterpenes can be synthesized using the CYP51 clan (Zhu et al., 2006; Geisler et al., 2013; Anusha et al., 2015; Lepesheva et al., 2015). The widely used anti-cancer agent taxol, which is the prime bioactive component of the Taxus species, is biosynthesized with CYP enzymes. A 2017 study focused on classifying the CYP enzymes from Taxus chinensis revealed the presence of 52 genes from CYP71 clan. Six genes from CYP725s were also identified, which are potential candidates for biosynthetic application. In addition, two gymnosperm specific families were discovered, namely CYP86 and CYP947. Knowledge on the presence of these CYPs can be important in developing new and cost effective industrial biosynthetic pathway for taxol synthesis (Liao et al., 2017). Research has been undertaken to find the biosynthetic pathway for drug synthesis, where CYPs act as a catalytic enzyme in the intermediary step. This will allow better understanding of the process, leading to optimize and accelerate the biotechnological production of complex natural products. For example, production of ingenol mebutate for actinic keratosis could be obtained from Euphorbia lathyris L., utilizing CYP71D445 and CYP726A27 (Luo et al., 2016). Production of ingenol metabutate from plant extraction or chemical synthesis is inefficient and expensive, limitations, which can be overcome by utilizing the newly found biosynthetic pathway (Luo et al., 2016).
Oral bioavailability and pharmacokinetics of esculetin following intravenous and oral administration in rats
Published in Xenobiotica, 2021
Jae-Hwan Kwak, Younghwa Kim, Christine E. Staatz, In-hwan Baek
Esculetin (6,7-dihydroxycoumarin) is the main active ingredient that is isolated from Artemisia montana (Nakai) Pamp. and Euphorbia lathyris L. (Kim et al.2000, Masamoto et al.2003). Artemisia montana (Nakai) Pamp. is a well-known Asian herbal medicine used to treat haemorrhoids, hepatotoxicity, hyperglycaemia, hypertension and fever (Kim et al.2000, Ahuja et al.2011). Euphorbia lathyris L., which is a common traditional Chinese medicine, has been used to treat amenorrhoea, constipation, hemodynamic dysfunctions, schistosomiasis, scabies and snake poison (Hou et al.2011, Lu et al.2014). Also, esculetin is a bioactive coumarin of Cortex Fraxini (dried bark of Fraxinus rhynchophylla Hance, Fraxinus chinensis Roxb., Fraxinus chinensis var. acuminata Lingelsh. and Fraxinus fallax Lingelsh.) which has been used for the clinical treatment of arthritis, bacillary dysentery, gout and hyperuricaemia (Wu et al.2007, Wang et al.2016). Isolated esculetin is known to have anticancer, anti-obesity, antioxidant, anti-proliferative, anti-inflammatory and neuroprotective activities (Huang et al.1993, Martín-Aragón et al.1998, Witaicenis et al.2010, Wang et al.2012, Anand et al.2013, Kim and Lee 2015).