Inhibition of thymidylate synthase and cell growth by the phenanthroindolizidine alkaloids pergularinine and tylophorinidine
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2020, Journal of EthnopharmacologyCitation Excerpt :Thymidylate synthase is an enzyme that plays a pivotal role in de novo DNA (Deoxyribonucleic acid) synthesis and found in elevated levels in malignant cells. Tylophorinidine has been advocated to inhibit thymidylate synthase in an in vitro enzyme study with IC50 value of 45 μM (Shahzad et al., 2016; Rao et al., 1997). Besides this, DHFR (Dihydro folate reductase) an important enzyme for synthesis of purines and pyrmidine precursors is also found elevated in malignant cells.
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2018, European Journal of Medicinal ChemistryCitation Excerpt :Due to their structural complexity in the creation of four stereo centres at C ring, it is difficult task to prepare their analogues from easily available raw materials [20]. However, the stereo chemical complexity can be minimized by elimination of C-2 and C-3 stereogenic carbons [21]. In this context, a number of medicinal chemists made considerable efforts towards the development of 4-aza podophyllotoxin (7) and its derivatives (Fig. 1) to retain the similar cytotoxicity to that of podophyllotoxin [22].
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