Thesis (M.Sc. (Chemistry)) -- University of Limpopo, 2020 / In an attempt to synthesise quinoxaline-ferrocene compounds with antimycobacterial
activity; a series of quinoxaline alkynyl derivatives were successfully synthesised from 3-
(quinoxalin-3-yl)prop-2-yn-1-ol 86A and 3-(6-chloroquinoxalin-2-yl)prop-2-yn-1-ol 86B. In
this series compounds 87A – B, 90A – B, and 93A – C were intermediates obtained in
an effort to synthesise quinoxaline-ferrocene compounds. Treatment of either 86A or 86B
with various acid chlorides afforded quinoxaline alkynyl ester derivatives 97A - 97B.
Within this series, two quinoxaline-ferrocene compounds 3-(quinoxalin-3-yl)prop-2-ynyl
ferrocetate 97A-iv and 3-(6-chloroquinoxalin-2-yl)prop-2-ynyl ferrocetate 97B-iv were
successfully incorporated with ferrocenoyl chloride and obtained in 42 - 43% yield. The
reactions of 3-chloroquinoxaline-2-carbonyl chloride 99 with ferrocenyl alcohol and
ferrocenyl amine were unsuccessful. However, 3-chloroquinoxaline-2-carbonyl ester
100A - C and amide 101A - D derivatives with various alcohols and amines were
obtained. The structures of all the compounds were confirmed by spectroscopic analysis
(NMR, FT-IR and HRMS).
The synthesised compounds were all evaluated for preliminary in-vitro antimycobacterial
activity. The results obtained exhibited compound 90B with the highest activity against
Mtb H37RV strain at MIC90 of 1.13 µM, followed by 90A and 87A exhibiting MIC90 of 4.55
and 6.47 µM, respectively. The quinoxaline alkynyl ester derivatives were found to exhibit
poor to good activity. Within this series, three compounds were found to exhibit
antimycobacterial activity at MIC90 ˂ 20 µM with compound 97A-ii showing the highest
activity at MIC90 of 16.18 µM, followed by 97A-i and 97B-iii showing MIC90 of 18.05 and
19.36 µM, respectively. From the two quixonaline-ferrocene compounds, compound 97A iv was found to exhibit antimycobacterial activity at MIC90 of 39.90 µM. However,
compound 97B-iv was found to be inactive. The 3-chloroquinoxaline-2-carbonyl ester
100A - C and amide 101A - D derivatives were found to be inactive. However, compound
99-C was found to exhibit antimycobacterial activity at MIC90 of 40.66 µM.
Compounds 86A, 86C, 87A and 90A were evaluated for in-vitro antiproliferative activity
against cancer cell lines. The results of antiproliferative activity showed that compounds
86A and 87A exhibited excellent activity against A549 lung cancer cell lines. Compound
87A was found to be the most active against A549 cell line showing 50% viability-inhibition
at 25 µM / National Research Foundation (NRF)
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:ul/oai:ulspace.ul.ac.za:10386/3377 |
| Date | January 2019 |
| Creators | Raphoko, Lerato Augustinah |
| Contributors | Nxumalo, W. |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | xvii, 108 leaves |
| Relation |
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