1. Novel extraction method based on the dispersion of the extraction solvent for extraction of letrozole from biological ﬂuids
Mohammad Rezaee, Yadollah Yamini,* Mohammad Hojjati and Mohammad Faraji. Anal. Methods, 2010, 2, 1341–1345
The goal of this work is to assess whether DLLME can be used as a valuable sample concentration approach for the determination of letrozole in biological ﬂuids and water samples using high-performance liquid chromatography (HPLC) analysis. Letrozole was used as the model compound in the development and evaluation of the procedure. Letrozole, (4, 4’-[1H-1,2,4-triazol-1-yl-methylene]bis-benzonitrile), is a selective nonsteroidal inhibitor of the aromatase system (oesterogen synthetase), that is used for the treatment of oesterogen dependency in breast cancer patients. The chemical structure of letrozole is shown in Fig. 1. Letrozole is readily and completely absorbed in the gastrointestinal tract. It is slowly metabolized in the liver to an inactive carbinol metabolite, which is then excreted as glucoronide in the urine.Several analytical methods have been presented for quantiﬁcation of letrozole in plasma samples.The inﬂuence of extractant and disperser solvents, as well as ionic strength, on the performance of this method, is discussed in detail later.
2. Synthesis and biological evaluation of imidazolylmethylacridones as cytochrome P-450 enzymes inhibitors
Ashraf H. Abadi,*Sahar M. Abou-Seri, Qingzhong Hu, Matthias Negri and Rolf W. Hartmann. Med. Chem.Common., 2012, 3, 663–666
Also, letrozole (2) was found to have the triazole sp2 N pointing perpendicular to the heme iron and p-stacked with Phe134, Phe221 and Trp224. One of the p-CN-phenyl rings pointed towards the hydrophobic loop opposite to the I-helix, while the other p-CN-phenyl ring was placed on the left of the C-terminal loop. Contrary to 5, a hydrogen bond was formed between the nitrile N and the backbone NH of Met374 and not with the –OH of Ser478. However, changing the crystallographic rotamer of Ser478 resulted in the formation of a second hydrogen bond, this time between the nitrile of the second p-CN-phenyl and Ser478.
3. Flavans from Desmos cochinchinensis as potent aromatase inhibitors
Vilailak Prachyawarakorn,* Suwannee Sangpetsiripan, Prasat Kittakoop*. Med. Chem. Commun., 2013, 4,1590–1596
The inhibition of aromatase was evaluated using the method reported by Stresser and co-workers. The reference compound was letrozole (Table 2). The cytotoxicity for adhesive cell lines, including the HuCCA-1, HepG2, and A549 cancer cell lines, was evaluated with the MTT assay, while the cytotoxicity for the non-adhesive MOLT-3 cell line was assessed using the XTT assay. Doxorubicin and etoposide were used as the reference drugs; doxorubicin exhibited cytotoxic activity against HuCCA-1 and A549 cells with IC50 values of 1.10 and 0.90μm, respectively, while etoposide displayed respective IC50 values of 22.11 and 0.03 μm towards the HepG2 and MOLT-3 cell lines (ESI, Table S1).
4. Synthetic methodologies of achiral diarylmethanols, diaryl and triarylmethanes (TRAMs) and medicinal properties of diaryl and triarylmethanes-an overview
Sankalan Mondal and Gautam Panda*. RSC Adv.,2014, 4,28317–28358
B. V. L. Potter et al. in 2005 reported letrozole based dual aromatase-sulphatase inhibitors. They incorporated the pharmacophore of the sulfatase inhibitors to the Letrozole core. In 2007 they reported the synthesis and bioevaluation of novel diarylmethane based dual aromatase-sulfatase inhibitors based on the anastrozole template (Fig. 12a). In 2008 the same group further improved on the bioactivity of the dual aromatase sulfatase inhibitors by reporting enantiopure non-steroidal inhibitors (Fig. 12b). The authors found that (64) was the most potent aromatase inhibitor. Interestingly they reported that the (R) isomer was a potent aromatase inhibitor while the (S) isomer was a potent sulfatase inhibitor. Later in the year 2010 they reported single compound dual inhibitors of the aromatase and steroid sulfatase enzymes.