NMR structural elucidation of channaine, an unusual alkaloid from Sceletium tortuosum:
- Veale, Clinton G L, Chen, Weiyang, Chaudhary, Sushil, Kituyi, Sarah N, Isaacs, Michelle, Hoppe, Heinrich C, Edkins, Adrienne L, Combrinck, Sandra, Mehari, Bewketu, Viljoen, Alvaro
- Authors: Veale, Clinton G L , Chen, Weiyang , Chaudhary, Sushil , Kituyi, Sarah N , Isaacs, Michelle , Hoppe, Heinrich C , Edkins, Adrienne L , Combrinck, Sandra , Mehari, Bewketu , Viljoen, Alvaro
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164345 , vital:41110 , DOI: 10.1016/j.phytol.2017.11.018
- Description: Chemical interrogation of the Sceletium genus and Amaryllidaceae family of plants has yielded a diverse array of aryl-hydroindole containing alkaloids. Included in this class is channaine, which was tentatively identified, without comprehensive structural elucidation from Sceletium tortuosum in 1957. Following its isolation from S. strictum, the structure of channaine was eventually resolved by X-ray crystallographic analysis, which revealed an unusual cage-like ring structure at the interface of two aryl-hydroindole subunits. However, since this report in 1978, channaine has not re-appeared in the literature. In this letter, the full NMR characterisation of channaine, isolated from S. tortuosum collected from St Helena in the Western Cape Province of South Africa, is reported for the first time.
- Full Text:
- Date Issued: 2018
- Authors: Veale, Clinton G L , Chen, Weiyang , Chaudhary, Sushil , Kituyi, Sarah N , Isaacs, Michelle , Hoppe, Heinrich C , Edkins, Adrienne L , Combrinck, Sandra , Mehari, Bewketu , Viljoen, Alvaro
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164345 , vital:41110 , DOI: 10.1016/j.phytol.2017.11.018
- Description: Chemical interrogation of the Sceletium genus and Amaryllidaceae family of plants has yielded a diverse array of aryl-hydroindole containing alkaloids. Included in this class is channaine, which was tentatively identified, without comprehensive structural elucidation from Sceletium tortuosum in 1957. Following its isolation from S. strictum, the structure of channaine was eventually resolved by X-ray crystallographic analysis, which revealed an unusual cage-like ring structure at the interface of two aryl-hydroindole subunits. However, since this report in 1978, channaine has not re-appeared in the literature. In this letter, the full NMR characterisation of channaine, isolated from S. tortuosum collected from St Helena in the Western Cape Province of South Africa, is reported for the first time.
- Full Text:
- Date Issued: 2018
Novobiocin–ferrocene conjugates possessing anticancer and antiplasmodial activity independent of HSP90 inhibition.
- Mbaba, Mziyanda, de la Mare, Jo-Anne, Sterrenberg, Jason N, Kajewole, Deborah, Maharaj, Shantal, Edkins, Adrienne L, Isaacs, Michelle, Hoppe, Heinrich C, Khanye, Setshaba D
- Authors: Mbaba, Mziyanda , de la Mare, Jo-Anne , Sterrenberg, Jason N , Kajewole, Deborah , Maharaj, Shantal , Edkins, Adrienne L , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122858 , vital:35359 , https://doi.org/10.1007/s00775-018-1634-9
- Description: A series of tailored novobiocin–ferrocene conjugates was prepared in moderate yields and investigated for in vitro anticancer and antiplasmodial activity against the MDA-MB-231 breast cancer line and Plasmodium falciparum 3D7 strain, respectively. While the target compounds displayed moderate anticancer activity against the breast cancer cell line with IC50 values in the mid-micromolar range, compounds 10a–c displayed promising antiplasmodial activity as low as 0.889 µM. Furthermore, the most promising compounds were tested for inhibitory effects against a postulated target, heat shock protein 90 (Hsp90).
- Full Text:
- Authors: Mbaba, Mziyanda , de la Mare, Jo-Anne , Sterrenberg, Jason N , Kajewole, Deborah , Maharaj, Shantal , Edkins, Adrienne L , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122858 , vital:35359 , https://doi.org/10.1007/s00775-018-1634-9
- Description: A series of tailored novobiocin–ferrocene conjugates was prepared in moderate yields and investigated for in vitro anticancer and antiplasmodial activity against the MDA-MB-231 breast cancer line and Plasmodium falciparum 3D7 strain, respectively. While the target compounds displayed moderate anticancer activity against the breast cancer cell line with IC50 values in the mid-micromolar range, compounds 10a–c displayed promising antiplasmodial activity as low as 0.889 µM. Furthermore, the most promising compounds were tested for inhibitory effects against a postulated target, heat shock protein 90 (Hsp90).
- Full Text:
Plasmodium falciparum Hep1 is required to prevent the self aggregation of PfHsp70-3
- Nyakundi, David O, Vuko, Loyiso A M, Bentley, Stephen J, Hoppe, Heinrich C, Blatch, Gregory L, Boshoff, Aileen
- Authors: Nyakundi, David O , Vuko, Loyiso A M , Bentley, Stephen J , Hoppe, Heinrich C , Blatch, Gregory L , Boshoff, Aileen
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66109 , vital:28903 , https://doi.org/10.1371/journal.pone.0156446
- Description: publisher version , The majority of mitochondrial proteins are encoded in the nucleus and need to be imported from the cytosol into the mitochondria, and molecular chaperones play a key role in the efficient translocation and proper folding of these proteins in the matrix. One such molecular chaperone is the eukaryotic mitochondrial heat shock protein 70 (Hsp70); however, it is prone to self-aggregation and requires the presence of an essential zinc-finger protein, Hsp70-escort protein 1 (Hep1), to maintain its structure and function. PfHsp70-3, the only Hsp70 predicted to localize in the mitochondria of P. falciparum, may also rely on a Hep1 orthologue to prevent self-aggregation. In this study, we identified a putative Hep1 orthologue in P. falciparum and co-expression of PfHsp70-3 and PfHep1 enhanced the solubility of PfHsp70-3. PfHep1 suppressed the thermally induced aggregation of PfHsp70-3 but not the aggregation of malate dehydrogenase or citrate synthase, thus showing specificity for PfHsp70-3. Zinc ions were indeed essential for maintaining the function of PfHep1, as EDTA chelation abrogated its abilities to suppress the aggregation of PfHsp70-3. Soluble and functional PfHsp70-3, acquired by co-expression with PfHep-1, will facilitate the biochemical characterisation of this particular Hsp70 protein and its evaluation as a drug target for the treatment of malaria. , This work was funded by grants from the National Research Foundation (NRF); grant number 87663 and Deutsche Forschungsgemeinschaft (DFG); grant number LI 402/14-1. D.O.N. is the recipient of academic development and training funds from Mwenge Catholic University, Moshi, Tanzania. S.J.B. is the recipient of an NRF Doctoral Innovation Scholarship.
- Full Text:
- Date Issued: 2016
- Authors: Nyakundi, David O , Vuko, Loyiso A M , Bentley, Stephen J , Hoppe, Heinrich C , Blatch, Gregory L , Boshoff, Aileen
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66109 , vital:28903 , https://doi.org/10.1371/journal.pone.0156446
- Description: publisher version , The majority of mitochondrial proteins are encoded in the nucleus and need to be imported from the cytosol into the mitochondria, and molecular chaperones play a key role in the efficient translocation and proper folding of these proteins in the matrix. One such molecular chaperone is the eukaryotic mitochondrial heat shock protein 70 (Hsp70); however, it is prone to self-aggregation and requires the presence of an essential zinc-finger protein, Hsp70-escort protein 1 (Hep1), to maintain its structure and function. PfHsp70-3, the only Hsp70 predicted to localize in the mitochondria of P. falciparum, may also rely on a Hep1 orthologue to prevent self-aggregation. In this study, we identified a putative Hep1 orthologue in P. falciparum and co-expression of PfHsp70-3 and PfHep1 enhanced the solubility of PfHsp70-3. PfHep1 suppressed the thermally induced aggregation of PfHsp70-3 but not the aggregation of malate dehydrogenase or citrate synthase, thus showing specificity for PfHsp70-3. Zinc ions were indeed essential for maintaining the function of PfHep1, as EDTA chelation abrogated its abilities to suppress the aggregation of PfHsp70-3. Soluble and functional PfHsp70-3, acquired by co-expression with PfHep-1, will facilitate the biochemical characterisation of this particular Hsp70 protein and its evaluation as a drug target for the treatment of malaria. , This work was funded by grants from the National Research Foundation (NRF); grant number 87663 and Deutsche Forschungsgemeinschaft (DFG); grant number LI 402/14-1. D.O.N. is the recipient of academic development and training funds from Mwenge Catholic University, Moshi, Tanzania. S.J.B. is the recipient of an NRF Doctoral Innovation Scholarship.
- Full Text:
- Date Issued: 2016
Potential repurposing of four FDA approved compounds with antiplasmodial activity identified through proteome scale computational drug discovery and in vitro assay
- Diallo, Bakary N, Swart, Tarryn, Hoppe, Heinrich C, Tastan Bishop, Özlem, Lobb, Kevin A
- Authors: Diallo, Bakary N , Swart, Tarryn , Hoppe, Heinrich C , Tastan Bishop, Özlem , Lobb, Kevin A
- Date: 2021
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/177531 , vital:42830 , https://doi.org/10.1038/s41598-020-80722-2
- Description: Malaria elimination can benefit from time and cost-efficient approaches for antimalarials such as drug repurposing. In this work, 796 DrugBank compounds were screened against 36 Plasmodium falciparum targets using QuickVina-W. Hits were selected after rescoring using GRaph Interaction Matching (GRIM) and ligand efficiency metrics: surface efficiency index (SEI), binding efficiency index (BEI) and lipophilic efficiency (LipE). They were further evaluated in Molecular dynamics (MD). Twenty-five protein–ligand complexes were finally retained from the 28,656 (36×796) dockings.
- Full Text:
- Date Issued: 2021
- Authors: Diallo, Bakary N , Swart, Tarryn , Hoppe, Heinrich C , Tastan Bishop, Özlem , Lobb, Kevin A
- Date: 2021
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/177531 , vital:42830 , https://doi.org/10.1038/s41598-020-80722-2
- Description: Malaria elimination can benefit from time and cost-efficient approaches for antimalarials such as drug repurposing. In this work, 796 DrugBank compounds were screened against 36 Plasmodium falciparum targets using QuickVina-W. Hits were selected after rescoring using GRaph Interaction Matching (GRIM) and ligand efficiency metrics: surface efficiency index (SEI), binding efficiency index (BEI) and lipophilic efficiency (LipE). They were further evaluated in Molecular dynamics (MD). Twenty-five protein–ligand complexes were finally retained from the 28,656 (36×796) dockings.
- Full Text:
- Date Issued: 2021
Quinolone-isoniazid hybrids: Synthesis and preliminary in vitro cytotoxicity and anti-tuberculosis evaluation
- Beteck, Richard M, Seldon, Ronnett, Khanye, Setshaba D, Legoabe, Lesetja J, Hoppe, Heinrich C, Laming, Dustin, Jordaan, Audrey, Warner, Digby F
- Authors: Beteck, Richard M , Seldon, Ronnett , Khanye, Setshaba D , Legoabe, Lesetja J , Hoppe, Heinrich C , Laming, Dustin , Jordaan, Audrey , Warner, Digby F
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123151 , vital:35410 , https://doi.org/10.1039/C8MD00480C
- 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: 2019
- Authors: Beteck, Richard M , Seldon, Ronnett , Khanye, Setshaba D , Legoabe, Lesetja J , Hoppe, Heinrich C , Laming, Dustin , Jordaan, Audrey , Warner, Digby F
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123151 , vital:35410 , https://doi.org/10.1039/C8MD00480C
- 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: 2019
Repurposing a polymer precursor: Synthesis and in vitro medicinal potential of ferrocenyl 1, 3-benzoxazine derivatives
- 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
- 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.
- Full Text:
- Date Issued: 2020
- 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.
- Full Text:
- Date Issued: 2020
Synthesis and anti-parasitic activity of C-benzylated (N-arylcarbamoyl) alkylphosphonate esters
- Adeyemi, Christiana Modupe, Isaacs, Michelle, Mnkandhla, Dumisani, Krause, Rui W M, Klein, Rosalyn, Hoppe, Heinrich C, Lobb, Kevin A, Kaye, Perry T
- Authors: Adeyemi, Christiana Modupe , Isaacs, Michelle , Mnkandhla, Dumisani , Krause, Rui W M , Klein, Rosalyn , Hoppe, Heinrich C , Lobb, Kevin A , Kaye, Perry T
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125641 , vital:35803 , https://doi.org/10.1016/j.tet.2017.01.045
- Description: Unexpected substituent-dependent regioselectivty challenges in the synthesis of C-benzylated (N-arylcarbamoyl)phosphonate esters have been resolved. The C-benzylated N-furfurylcarbamoyl derivative showed low micromolar PfLDH inhibition, while one of the C-benzylated N-arylcarbamoyl analogues was active against Nagana Trypanosoma brucei parasites which are responsible for African trypanosomiasis in cattle.
- Full Text:
- Date Issued: 2017
- Authors: Adeyemi, Christiana Modupe , Isaacs, Michelle , Mnkandhla, Dumisani , Krause, Rui W M , Klein, Rosalyn , Hoppe, Heinrich C , Lobb, Kevin A , Kaye, Perry T
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125641 , vital:35803 , https://doi.org/10.1016/j.tet.2017.01.045
- Description: Unexpected substituent-dependent regioselectivty challenges in the synthesis of C-benzylated (N-arylcarbamoyl)phosphonate esters have been resolved. The C-benzylated N-furfurylcarbamoyl derivative showed low micromolar PfLDH inhibition, while one of the C-benzylated N-arylcarbamoyl analogues was active against Nagana Trypanosoma brucei parasites which are responsible for African trypanosomiasis in cattle.
- Full Text:
- Date Issued: 2017
Synthesis and evaluation of substituted 4-(N-benzylamino)cinnamate esters as potential anti-cancer agents and HIV-1 integrase inhibitors
- Faridoon, H, Edkins, Adrienne L, Isaacs, Michelle, Mnkandhla, Dumisani, Hoppe, Heinrich C, Kaye, Perry T
- Authors: Faridoon, H , Edkins, Adrienne L , Isaacs, Michelle , Mnkandhla, Dumisani , Hoppe, Heinrich C , Kaye, Perry T
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66289 , vital:28929 , https://doi.org/10.1016/j.bmcl.2016.05.023
- Description: publisher version , Encouraging selectivity and low micromolar activity against HeLa cervical carcinoma (IC50 ⩾ 3.0 μM) and the aggressive MDA-MB-231 triple negative breast carcinoma (IC50 ⩾ 9.6 μM) cell lines has been exhibited by a number of readily accessible 4-(N-benzylamino)cinnamate esters. The potential of the ligands as HIV-1 integrase inhibitors has also been examined.
- Full Text: false
- Date Issued: 2016
- Authors: Faridoon, H , Edkins, Adrienne L , Isaacs, Michelle , Mnkandhla, Dumisani , Hoppe, Heinrich C , Kaye, Perry T
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66289 , vital:28929 , https://doi.org/10.1016/j.bmcl.2016.05.023
- Description: publisher version , Encouraging selectivity and low micromolar activity against HeLa cervical carcinoma (IC50 ⩾ 3.0 μM) and the aggressive MDA-MB-231 triple negative breast carcinoma (IC50 ⩾ 9.6 μM) cell lines has been exhibited by a number of readily accessible 4-(N-benzylamino)cinnamate esters. The potential of the ligands as HIV-1 integrase inhibitors has also been examined.
- Full Text: false
- Date Issued: 2016
Synthesis, antiplasmodial and antitrypanosomal evaluation of a series of novel 2-oxoquinoline-based thiosemicarbazone derivatives
- Darrell, Oliver T, Hulushe, Siyabonga T, Mtshare, Thanduxolo Elihle, Beteck, Richard M, Isaacs, Michelle, Laming, Dustin, Khanye, Setshaba D, Hoppe, Heinrich C, Krause, Rui W M
- Authors: Darrell, Oliver T , Hulushe, Siyabonga T , Mtshare, Thanduxolo Elihle , Beteck, Richard M , Isaacs, Michelle , Laming, Dustin , Khanye, Setshaba D , Hoppe, Heinrich C , Krause, Rui W M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123117 , vital:35407 , https://doi.org/10.17159/0379-4350/2018/v71a25
- Description: Herein a series of novel thiosemicarbazones (TSCs) derived from 2-oxoquinoline scaffold is reported, and the target compounds have been successfully synthesized and characterized using standard spectroscopic techniques. The in vitro biological activities of synthesized molecules were evaluated against Plasmodium falciparum malaria parasites (strain 3D7), Trypanosoma brucei brucei parasites (strain 427) and HeLa cells. All the compounds displayed modest or no activity at a concentration of 20 μM and percentage viability of >50 % was often observed. Except for compound 9o, none of the final compounds exhibited cytotoxic effects against HeLa cells at 20 μM.
- Full Text:
- Date Issued: 2018
- Authors: Darrell, Oliver T , Hulushe, Siyabonga T , Mtshare, Thanduxolo Elihle , Beteck, Richard M , Isaacs, Michelle , Laming, Dustin , Khanye, Setshaba D , Hoppe, Heinrich C , Krause, Rui W M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123117 , vital:35407 , https://doi.org/10.17159/0379-4350/2018/v71a25
- Description: Herein a series of novel thiosemicarbazones (TSCs) derived from 2-oxoquinoline scaffold is reported, and the target compounds have been successfully synthesized and characterized using standard spectroscopic techniques. The in vitro biological activities of synthesized molecules were evaluated against Plasmodium falciparum malaria parasites (strain 3D7), Trypanosoma brucei brucei parasites (strain 427) and HeLa cells. All the compounds displayed modest or no activity at a concentration of 20 μM and percentage viability of >50 % was often observed. Except for compound 9o, none of the final compounds exhibited cytotoxic effects against HeLa cells at 20 μM.
- Full Text:
- Date Issued: 2018
Synthesis, characterization and biological activity of some Dithiourea Derivatives:
- Odame, Felix, Hosten, Eric, Krause, Jason, Isaacs, Michelle, Hoppe, Heinrich C, Khanye, Setshaba D, Sayed, Yasien, Frost, Carminita, Lobb, Kevin A, Tshentu, Zenixole
- Authors: Odame, Felix , Hosten, Eric , Krause, Jason , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D , Sayed, Yasien , Frost, Carminita , Lobb, Kevin A , Tshentu, Zenixole
- 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
- Authors: Odame, Felix , Hosten, Eric , Krause, Jason , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D , Sayed, Yasien , Frost, Carminita , Lobb, Kevin A , Tshentu, Zenixole
- 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
Synthesis, in vitro cytotoxicity and trypanocidal evaluation of novel 1, 3, 6-substituted non-fluoroquinolones
- Beteck, Richard M, Isaacs, Michelle, Khanye, Setshaba D, Hoppe, Heinrich C
- Authors: Beteck, Richard M , Isaacs, Michelle , Khanye, Setshaba D , Hoppe, Heinrich C
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123140 , vital:35409 , https://doi.org/10.17159/0379-4350/2018/v71a25
- Description: Sleeping sickness (trypanosomiasis) is a neglected tropical disease that affects mostly the poorest communities in sub-Saharan Africa. Toxic side effects associated with the use of current anti-trypanosomal drugs, which in some cases kill faster than the disease itself, necessitate the search for new drugs with better safety margins. To this effect, a small library bearing different substituents at position -1, -3, and -6 of the quinolone nucleus were synthesized and evaluated in vitro against HeLa cell lines and Trypanosoma brucei brucei for cytotoxicity and trypanocidal potentials, respectively. While most of these compounds showed no cytotoxic effect, they exhibited moderate to weak anti-trypanosomal activities. The SAR studies of this series provide new information worth considering in future exploration of the quinolone scaffold in search ofmore potent and safe trypanocidal agents.
- Full Text:
- Date Issued: 2018
- Authors: Beteck, Richard M , Isaacs, Michelle , Khanye, Setshaba D , Hoppe, Heinrich C
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123140 , vital:35409 , https://doi.org/10.17159/0379-4350/2018/v71a25
- Description: Sleeping sickness (trypanosomiasis) is a neglected tropical disease that affects mostly the poorest communities in sub-Saharan Africa. Toxic side effects associated with the use of current anti-trypanosomal drugs, which in some cases kill faster than the disease itself, necessitate the search for new drugs with better safety margins. To this effect, a small library bearing different substituents at position -1, -3, and -6 of the quinolone nucleus were synthesized and evaluated in vitro against HeLa cell lines and Trypanosoma brucei brucei for cytotoxicity and trypanocidal potentials, respectively. While most of these compounds showed no cytotoxic effect, they exhibited moderate to weak anti-trypanosomal activities. The SAR studies of this series provide new information worth considering in future exploration of the quinolone scaffold in search ofmore potent and safe trypanocidal agents.
- Full Text:
- Date Issued: 2018
Synthesis, structure and in vitro anti-trypanosomal activity of non-toxic Arylpyrrole-Based Chalcone derivatives:
- Zulu, Ayanda I, Oderinlo, Ogunyemi O, Kruger, Cuan, Isaacs, Michelle, Hoppe, Heinrich C, Smith, Vincent J, Veale, Clinton G L, Khanye, Setshaba D
- Authors: Zulu, Ayanda I , Oderinlo, Ogunyemi O , Kruger, Cuan , Isaacs, Michelle , Hoppe, Heinrich C , Smith, Vincent J , Veale, Clinton G L , Khanye, Setshaba D
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/179017 , vital:40096 , https://doi.org/10.3390/molecules25071668
- Description: With an intention of identifying chalcone derivatives exhibiting anti-protozoal activity, a cohort of relatively unexplored arylpyrrole-based chalcone derivatives were synthesized in moderate to good yields. The resultant compounds were evaluated in vitro for their potential activity against a cultured Trypanosoma brucei brucei 427 strain. Several compounds displayed mostly modest in vitro anti-trypanosomal activity with compounds 10e and 10h emerging as active candidates with IC50 values of 4.09 and 5.11 µM, respectively. More importantly, a concomitant assessment of their activity against a human cervix adenocarcinoma (HeLa) cell line revealed that these compounds are non-toxic.
- Full Text:
- Date Issued: 2020
- Authors: Zulu, Ayanda I , Oderinlo, Ogunyemi O , Kruger, Cuan , Isaacs, Michelle , Hoppe, Heinrich C , Smith, Vincent J , Veale, Clinton G L , Khanye, Setshaba D
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/179017 , vital:40096 , https://doi.org/10.3390/molecules25071668
- Description: With an intention of identifying chalcone derivatives exhibiting anti-protozoal activity, a cohort of relatively unexplored arylpyrrole-based chalcone derivatives were synthesized in moderate to good yields. The resultant compounds were evaluated in vitro for their potential activity against a cultured Trypanosoma brucei brucei 427 strain. Several compounds displayed mostly modest in vitro anti-trypanosomal activity with compounds 10e and 10h emerging as active candidates with IC50 values of 4.09 and 5.11 µM, respectively. More importantly, a concomitant assessment of their activity against a human cervix adenocarcinoma (HeLa) cell line revealed that these compounds are non-toxic.
- Full Text:
- Date Issued: 2020
The in vitro antiplasmodial and antiproliferative activity of new ferrocene-based α-aminocresols targeting hemozoin inhibition and DNA interaction:
- 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
- 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.
- Full Text:
- Date Issued: 2020
- 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.
- Full Text:
- Date Issued: 2020