Rationally designed hecogenin thiosemicarbazone analogs as novel MEK inhibitors for the control of breast malignancies

Graviola (Annona muricata) Exerts Anti-Proliferative, Anti-Clonogenic and Pro-Apoptotic Effects in Human Non-Melanoma Skin Cancer UW-BCC1 and A431 Cells In Vitro: Involvement of Hedgehog Signaling

“…The PENDANT 13 C NMR spectroscopy method is a J-modulation polarization transfer carbon sequence in which methylene and quaternary carbons are aligned up while the methyl and methine carbons are aligned down [ 36 , 37 , 38 ]. When applied to the graviola DCM extract ( Figure 7 A), four different signal clusters are apparent: an upfield aliphatic methyl and methylene carbons (δ 0–40), a cluster containing oxygenated methylene and methine carbons (δ 60–80), a group of methylenedioxy, olefinic and/or aromatic carbons (δ 105–152), and finally a group of lactone/ester carbonyl and ketone carbons (δ 165–212).…”

Saponins and Sapogenins of Agave With Respect to Diverse Pharmacological Role of Hecogenin

“…In addition to this, hecogenin exhibits variety of important biological activities in the pharmaceutical industry [12,13]. The steroidal sapogenins (hecogenin) from Agave genus were reported to have a number of pharmacological activities such as anti-inflammatory, analgesic, antiarthritis, gastroprotective, anticancer and larvicidal activity [14][15][16][17][18]. Overall, the results of numerous pharmacological studies have been linking the possible use of hecogenin as a novel multi-target based therapeutic agent against abundant long-lasting disease conditions.…”

“…The treatment from cytotoxic chemotherapy has been surprising changed to successful molecular targeted cancer therapy, with significant safety [48]. Elsayed et al, (2017) have studied the anticancer effect of hecogenin thiosemicarbazone analogs as novel mitogen activated protein kinase/extracellular signal-regulated kinase (MEK) inhibitors for the control of breast cancer. In this study they have prepared thirty three analogs and tested on various in vitro (cell proliferation, cytotoxicity assay, lactate dehydrogenase release assay, migration assay, invasion assay, protein extraction and immunoblotting assay) and in vivo model (orthotopic xenograft model by using MDA-MB-231/GFP human breast cancer cells), among which hecogenin 12-(30-methylphenyl thiosemicarbazone) have demonstrated the most potent antiproliferative, anti-migratory and anti-invasive activities at low concentration level [18].…”

Graviola (<em>Annona muricata</em>) Exerts Anti-Proliferative, Anti-Clonogenic and Pro-Apoptotic Effects in Human Non-Melanoma Skin Cancer UW-BCC1 and A431 Cells <em>In Vitro:</em> Involvement of Hedgehog Signaling

“…1 H and 13 C/PENDANT FT NMR spectra were recorded at 400 and 100 MHz, respectively, on a JEOL Eclipse ECS-400 NMR spectrometer (JEOL Inc., Peabody, MA) equipped with a 5 mm FG/TH autotune probe in CD3Cl, except for the MeOH extract spectrum, which was acquired in CD3OD, using the residual solvent peak as internal reference [69][70][71]. A relaxation delay of 3 seconds was used in the PENDANT experiment instead of the default 2 seconds.…”

“…negative ion mode using Analyst version 1.4.1 software (MDS Sciex, Toronto, Canada) [69][70][71]. For MS, about mg of dry DCM extract was dissolved in mL of HPLC-grade methanol, filtered and used for analysis.…”