Cytotoxicity of triterpenoids from Clerodendrum glabrum against triple negative breast cancer cells in vitro:
- Authors: Teclegeorgish, Zecarias W , Mokgalaka, Ntebogeng S , Vukea, Nyeleti , de la Mare, Jo-Anne , Tembu, Vuyelwa J
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/161511 , vital:40634 , https://doi.org/10.1016/j.sajb.2020.07.009
- Description: Clerodendrum glabrum is an indigenous medicinal plant that is used to treat cough, cold, sore throat and chest complaints. The stem bark of Clerodendrum glabrum afforded four tritepenoids namely, 3β-olean-12-en-3-yl palmitate (β-amyrin palmitate), (1), 3β hydroxy 5-glutinene (glutinol), (2), 3β-lup-20(29)-en-3-palmitate (Lupeol-3-palmitate), (3), 3β-lup-20(29)-en-3-ol (lupeol) (4) and one common phytosterol (stigmasterol) (5). The structures were established on the basis of their spectroscopic analysis. The compounds were screened for cytotoxicity against the HCC70 triple negative breast cancer (TNBC), MCF-7 hormone receptor positive breast cancer and MCF-12A non-cancerous mammary epithelial cell lines.
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- Date Issued: 2020
Repurposing a polymer precursor: Synthesis and in vitro medicinal potential of ferrocenyl 1, 3-benzoxazine derivatives
- Authors: Mbaba, Mziyanda , Dingle, Laura M K , Cash, Devon , de la Mare, Jo-Anne , Laming, Dustin , Taylor, Dale , Hoppe, Heinrich C , Edkins, Adrienne L , Khanye, Setshaba D
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165395 , vital:41240 , https://doi.org/10.1016/j.ejmech.2019.111924
- Description: Cancer and malaria remain relevant pathologies in modern medicinal chemistry endeavours. This is compounded by the threat of development of resistance to existing clinical drugs in use as first-line option for treatment of these diseases. To counter this threat, strategies such as drug repurposing and hybridization are constantly adapted in contemporary drug discovery for the expansion of the drug arsenal and generation of novel chemotypes with potential to avert or delay resistance. In the present study, a polymer precursor scaffold, 1,3-benzoxazine, has been repurposed by incorporation of an organometallic ferrocene unit to produce a novel class of compounds showing in vitro biological activity against breast cancer, malaria and trypanosomiasis.
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- Date Issued: 2020
Ruthenium complexes with mono-or bis-heterocyclic chelates: DNA/BSA binding, Antioxidant and Anticancer studies
- Authors: Maikoo, Sanam , Chakraborty, Abir , Vukea, Nyeleti , Dingle, Laura M K , Samson, William J , de la Mare, Jo-Anne , Edkins, Adrienne L , Booysen, Irvin N
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165463 , vital:41246 , DOI: 10.1080/07391102.2020.1775126
- Description: Deoxyribonucleic acid (DNA) and bovine serum albumin (BSA) binding interactions for a series of ruthenium heterocyclic complexes were monitored using ultraviolet-visible (UV-Vis) spectrophotometry, fluorescence emission spectroscopy and agarose gel electrophoresis. Investigations of the DNA interactions for the metal complexes revealed that they are groove-binders with intrinsic binding constants in the order of 104 – 107 M−1.
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- Date Issued: 2020
STIP1/HOP regulates the actin cytoskeleton through interactions with actin and changes in actin-binding proteins cofilin and profilin:
- Authors: Beckley, Samantha Joy , Hunter, Morgan C , Kituyi, Sarah N , Wingate, Ianthe , Chakraborty, Abantika , Schwarz, Kelly , Makhubu, Matodzi P , Rousseau, Robert P , Ruck, Duncan K , de la Mare, Jo-Anne , Blatch, Gregory L , Edkins, Adrienne L
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165373 , vital:41238 , https://doi.org/10.3390/ijms21093152
- Description: Cell migration plays a vital role in both health and disease. It is driven by reorganization of the actin cytoskeleton, which is regulated by actin-binding proteins cofilin and profilin. Stress-inducible phosphoprotein 1 (STIP1) is a well-described co-chaperone of the Hsp90 chaperone system, and our findings identify a potential regulatory role of STIP1 in actin dynamics. We show that STIP1 can be isolated in complex with actin and Hsp90 from HEK293T cells and directly interacts with actin in vitro via the C-terminal TPR2AB-DP2 domain of STIP1, potentially due to a region spanning two putative actin-binding motifs. We found that STIP1 could stimulate the in vitro ATPase activity of actin, suggesting a potential role in the modulation of F-actin formation. Interestingly, while STIP1 depletion in HEK293T cells had no major effect on total actin levels, it led to increased nuclear accumulation of actin, disorganization of F-actin structures, and an increase and decrease in cofilin and profilin levels, respectively. This study suggests that STIP1 regulates the cytoskeleton by interacting with actin, or via regulating the ratio of proteins known to affect actin dynamics.
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- Date Issued: 2020
The in vitro antiplasmodial and antiproliferative activity of new ferrocene-based α-aminocresols targeting hemozoin inhibition and DNA interaction:
- Authors: Mbaba, Mziyanda , Dingle, Laura M K , Swart, Tarryn , Cash, Devon , Laming, Dustin , de la Mare, Jo-Anne , Taylor, Dale , Hoppe, Heinrich C , Biot, Christophe , Edkins, Adrienne L , Khanye, Setshaba D
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/149347 , vital:38827 , https://0-doi.org.wam.seals.ac.za/10.1002/cbic.202000132
- Description: Compounds incorporating ferrocene in a aminocresol scaffold showed antiplasmodial and anticancer activity. SAR studies revealed that an OH group and rotatable C–NH bond are vital for biological activity, with spectrophotometric techniques and docking simulations suggesting a dual mode of action involving hemozoin inhibition and DNA interaction. Targeting multiple pathways could delay the development of clinical resistance.
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- Date Issued: 2020