Synthesis, characterization and biological activity of some Dithiourea Derivatives:
- Authors: Odame, Felix , Hosten, Eric C , Krause, Jason , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D , Sayed, Yasien , Frost, Carminita , Lobb, Kevin A , Tshentu, Zenixole R
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163046 , vital:41007 , DOI: 10.17344/acsi.2019.5689
- Description: Novel dithiourea derivatives have been designed as HIV-1 protease inhibitors using Autodock 4.2, synthesized and characterized by spectroscopic methods and microanalysis.
- Full Text:
- Date Issued: 2020
Purification and biochemical characterisation of a putative sodium channel agonist secreted from the South African Knobbly sea anemone Bunodosoma capense
- Authors: van Losenoord, Wynand , Krause, Jason , Parker-Nance, Shirley , Krause, Rui W M , Stoychey, Stoyan , Frost, Carminita L
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/194082 , vital:45421 , xlink:href="https://doi.org/10.1016/j.toxicon.2019.06.222"
- Description: Voltage gated ion channels have become a subject of investigation as possible pharmaceutical targets. Research has linked the activity of ion channels directly to anti-inflammatory pathways, energy homeostasis, cancer proliferation and painful diabetic neuropathy. Sea anemones secrete a diverse array of bioactive compounds including potassium and sodium channel toxins. A putative novel sodium channel agonist (molecular mass of 4619.7 Da) with a predicted sequence: CLCNSDGPSV RGNTLSGILW LAGCPSGWHN CKKHKPTIGW CCK was isolated from Bunodosoma capense using a modified stimulation technique to induce the secretion of the neurotoxin rich mucus confirmed by an Artemia nauplii bio-assay. The peptide purification combined size-exclusion and reverse-phase high performance liquid chromatography. A thallium-based ion flux assay confirmed the presence of a sodium channel agonist/inhibitor and purity was determined using a modified tricine SDS-PAGE system. The peptide isolated indicated the presence of multiple disulfide bonds in a tight β-defensin cystine conformation. An IC50 value of 26 nM was determined for total channel inhibition on MCF-7 cells. The unique putative sodium channel agonist initiating with a cystine bond indicates a divergent evolution to those previously isolated from Bunodosoma species.
- Full Text:
- Date Issued: 2019
A New Synthetic Method for Tetraazatricyclic Derivatives and Evaluation of Their Biological Properties
- Authors: Odame, Felix , Betz, Richard , Hosten, Eric C , Krause, Jason , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D , Sayed, Yasien , Frost, P Carminita , Lobb, Kevin A , Tshentu, Zenixole R
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123189 , vital:35413 , https://doi.org/10.1002/slct.201802930
- Description: Herein, we propose novel quinolones incorporating an INH moiety as potential drug templates against TB. The quinolone-based compounds bearing an INH moiety attached via a hydrazide–hydrazone bond were synthesised and evaluated against Mycobacterium tuberculosis H37Rv (MTB). The compounds were also evaluated for cytotoxicity against HeLa cell lines. These compounds showed significant activity (MIC90) against MTB in the range of 0.2–8 μM without any cytotoxic effects. Compounds 10 (MIC90; 0.9 μM), 11 (MIC90; 0.2 μM), 12 (MIC90; 0.8 μM) and compound 15 (MIC90; 0.8 μM), the most active compounds in this series, demonstrate activities on par with INH and superior to those reported for the fluoroquinolones. The SAR analysis suggests that the nature of substituents at positions −1 and −3 of the quinolone nucleus influences anti-MTB activity. Aqueous solubility evaluation and in vitro metabolic stability of compound 12 highlights favourable drug-like properties for this compound class.
- Full Text:
- Date Issued: 2018
Synthesis, characterization and DPPH scavenging activity of some benzimidazole derivatives
- Authors: Odame, Felix , Krause, Jason , Hosten, Eric C , Betz, Richard , Lobb, Kevin A , Tshentu, Zenixole R , Frost, Carminita L
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447209 , vital:74592 , xlink:href="https://dx.doi.org/10.4314/bcse.v32i2.8 "
- Description: A base-catalyzed conversion of aldehydes to benzimidazoles has been achieved. The compounds have been characterized by IR, NMR, micoranalysis, and GC-MS. The reaction for the formation of benzimidazoles has been monitored with 1 H NMR and IR. The crystal structures of two derivatives, 2-(2- chlorophenyl)-1H-benzimidazole and 2-(1H-benzimidazol-2-yl)-4-nitrophenol, are presented. A study of the DPPH scavenging activity of these compounds showed that 2-(1H-benzimidazol-2-yl)phenol (2), 2-p-tolyl-1Hbenzimidazole (3) and 2-(4-methoxyphenyl)-1H-benzimidazole (7) gave IC50 values 1974, 773 and 800 µM.
- Full Text:
- Date Issued: 2018