Antimalarial activity of quinoline thiosemicarbazones: synthesis and antiplasmodial evaluation
- Nqeno, Lukhanyiso Khanyisile
- Authors: Nqeno, Lukhanyiso Khanyisile
- Date: 2022-04-06
- Subjects: Antimalarials , Quinoline , Thiosemicarbazones , Malaria Chemotherapy , Plasmodium falciparum , Malaria Africa, Sub-Saharan , Iron chelates Therapeutic use
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/291292 , vital:56841
- Description: Africa is one of the regions that is most affected by malaria, as 90% of all malaria deaths occur in sub-saharan Africa. Malaria is a life threatening disease responsible for an estimated 800000 deaths each year, the majority of these deaths occurred in children under the age of five. The disease is a mosquito-borne, and it is transmitted to humans by the female Anopheles mosquito. The parasite responsible for this disease belong to the Plasmodium genus with Plasmodium falciparum causing the most severe cases of the disease in humans. The most widely available anti-malarials were designed to specifically target the pathogenic blood stage in humans, however, in order to completely eradicate malaria there is a need for the development of medicines that not only target the pathogenic blood stage of the parasite but also block parasite transmission and eliminate asymptomatic and cryptic hepatic forms of the parasite. Iron chelators have recently gained importance as potent antimalarials, to cause infection nearly all protozoa obtain growth essential iron from their hosts. Iron is required for the development of the parasite. Deprivation of utilizable iron by chelation is a proficient approach to arrest parasite growth and associated infection. Thiosemicarbazones are known iron chelating agents by bonding through the sulfur and azomethine nitrogen atoms. This study is aimed at the identification of thiosemicarbazone based derivatives as possible antimalarial agents. Due to their iron chelation abilities there has been increasing interest in the investigation of thiosemicarbazones as possible antimalarials. During the course of this project, several thiosemicarbazone derivatives were synthesized and their structure confirmed using routine analytical techniques (NMR, FTIR, and HRMS). The synthesized compounds were evaluated in vitro against the chloroquine sensitive strain (3D7) of P. falciparum for antimarial activity. The compounds were also evaluated agsinst Hela cells for overt cytotoxicity. The compounds generally showed poor antimalarial activity. One compound (LKN11) was identified to possess intrinsic and moderate antimalarial activity of 6.6 μM. The compounds were generally not cytotoxic against Hela cell at concentrations of up to 20 μM, with only compound LKN10 showing modest cytotoxic activity of 9.5 μM. This research went on to identify two thiosemicarbazone based derivatives which had a significant effect on HeLa and pLDH cells. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-06
- Authors: Nqeno, Lukhanyiso Khanyisile
- Date: 2022-04-06
- Subjects: Antimalarials , Quinoline , Thiosemicarbazones , Malaria Chemotherapy , Plasmodium falciparum , Malaria Africa, Sub-Saharan , Iron chelates Therapeutic use
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/291292 , vital:56841
- Description: Africa is one of the regions that is most affected by malaria, as 90% of all malaria deaths occur in sub-saharan Africa. Malaria is a life threatening disease responsible for an estimated 800000 deaths each year, the majority of these deaths occurred in children under the age of five. The disease is a mosquito-borne, and it is transmitted to humans by the female Anopheles mosquito. The parasite responsible for this disease belong to the Plasmodium genus with Plasmodium falciparum causing the most severe cases of the disease in humans. The most widely available anti-malarials were designed to specifically target the pathogenic blood stage in humans, however, in order to completely eradicate malaria there is a need for the development of medicines that not only target the pathogenic blood stage of the parasite but also block parasite transmission and eliminate asymptomatic and cryptic hepatic forms of the parasite. Iron chelators have recently gained importance as potent antimalarials, to cause infection nearly all protozoa obtain growth essential iron from their hosts. Iron is required for the development of the parasite. Deprivation of utilizable iron by chelation is a proficient approach to arrest parasite growth and associated infection. Thiosemicarbazones are known iron chelating agents by bonding through the sulfur and azomethine nitrogen atoms. This study is aimed at the identification of thiosemicarbazone based derivatives as possible antimalarial agents. Due to their iron chelation abilities there has been increasing interest in the investigation of thiosemicarbazones as possible antimalarials. During the course of this project, several thiosemicarbazone derivatives were synthesized and their structure confirmed using routine analytical techniques (NMR, FTIR, and HRMS). The synthesized compounds were evaluated in vitro against the chloroquine sensitive strain (3D7) of P. falciparum for antimarial activity. The compounds were also evaluated agsinst Hela cells for overt cytotoxicity. The compounds generally showed poor antimalarial activity. One compound (LKN11) was identified to possess intrinsic and moderate antimalarial activity of 6.6 μM. The compounds were generally not cytotoxic against Hela cell at concentrations of up to 20 μM, with only compound LKN10 showing modest cytotoxic activity of 9.5 μM. This research went on to identify two thiosemicarbazone based derivatives which had a significant effect on HeLa and pLDH cells. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-06
Exploring Quinolinyl-Thiazolidinedione hybrid compounds as potential anti-tubercular agents
- Authors: Mtshare, Thanduxolo Elihle
- Date: 2020
- Subjects: Quinoline , Mycobacterium tuberculosis , Tuberculosis -- Chemotherapy , Plasmodium falciparum , Thiazolidinedione
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/143314 , vital:38232
- Description: Tuberculosis (TB) is an infectious disease caused by the pathogen, Mycobacterium tuberculosis. According to the World Health Organization, TB is the ninth leading cause of death worldwide ranking above HIV/AIDS. This high mortality rate of TB begs the questions about the efficiency of the current therapy and raises an urgent need to create novel anti-tuberculosis agents which will aid in curbing this burden. Quinoline containing compounds have remarkable biological activities across a wide spectrum of diseases including anti-tuberculosis. On the other hand, thiazolidinedione containing compounds possess a broad spectrum of biological properties. In this study, we rationally designed compounds containing these pharmacophoric units and investigated them for their potential biological activity against Mycobacterium tuberculosis. Considering antimalarial activity of quinoline-based compounds, the compounds achieved were also cross-screened for their activity against the Plasmodium falciparum parasite, a causative agent of malaria. In all the synthesized compounds, compound 2.6a, 2.6b and 2.7b emerged as most active compounds against the H37Rv strain with MIC₉₀ values ranging in between of 1.08 – 17.1 μM. In addition, none of the compounds showed any inhibitory activities against the 3D7 strain of P. falciparum parasite. All the compounds prepared in this study showed no significant human cytotoxic effects as measured by HeLa cell line.
- Full Text:
- Date Issued: 2020
- Authors: Mtshare, Thanduxolo Elihle
- Date: 2020
- Subjects: Quinoline , Mycobacterium tuberculosis , Tuberculosis -- Chemotherapy , Plasmodium falciparum , Thiazolidinedione
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/143314 , vital:38232
- Description: Tuberculosis (TB) is an infectious disease caused by the pathogen, Mycobacterium tuberculosis. According to the World Health Organization, TB is the ninth leading cause of death worldwide ranking above HIV/AIDS. This high mortality rate of TB begs the questions about the efficiency of the current therapy and raises an urgent need to create novel anti-tuberculosis agents which will aid in curbing this burden. Quinoline containing compounds have remarkable biological activities across a wide spectrum of diseases including anti-tuberculosis. On the other hand, thiazolidinedione containing compounds possess a broad spectrum of biological properties. In this study, we rationally designed compounds containing these pharmacophoric units and investigated them for their potential biological activity against Mycobacterium tuberculosis. Considering antimalarial activity of quinoline-based compounds, the compounds achieved were also cross-screened for their activity against the Plasmodium falciparum parasite, a causative agent of malaria. In all the synthesized compounds, compound 2.6a, 2.6b and 2.7b emerged as most active compounds against the H37Rv strain with MIC₉₀ values ranging in between of 1.08 – 17.1 μM. In addition, none of the compounds showed any inhibitory activities against the 3D7 strain of P. falciparum parasite. All the compounds prepared in this study showed no significant human cytotoxic effects as measured by HeLa cell line.
- Full Text:
- Date Issued: 2020
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