No description available.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1953. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Inaug.-diss.-Würzburg. / Lebenslauf.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1962. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1965. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Coumarin compounds responsible for bitterness, and indirectly, toxicity, in the forage legume sweet clover (Melilotus alba) do not occur in the non-bitter "Cumino" variety of M. alba or in the species M. dentata. Nevertheless, investigation showed that compounds which are very probably coumarins do occur in the non-bitter strains. A search for coumarins in alfalfa (Medicago sativa), closely related to sweet clover taxonomically, did not lead to the discovery of coumarins but did lead to the characterization of a new flavonoid tentatively characterized as 3:3:4 trihydroxy -5:7 dimethoxy flavone. / Land and Food Systems, Faculty of / Graduate

No description available.

This thesis describes a biosynthetic investigation of coumarins in turpentine-broom, Thamnosma montana Torr. and Frem. In contrast to simple coumarins, the biosynthetic pathways leading to the furanocoumarins were found to be in a state of confusion as indicated by existing published data. None of the results were internally consistent with any general postulate and there was considerable question concerning the actual meaning of a substantial portion of the experimental data. Studies as described here were performed in several different areas. In the initial investigations, a detailed study of isolation procedures for the many coumarins present in the plant was necessary. Subsequently, appropriate chemical degradative pathways were developed for umbelliprenin (11), isopimpinellin (2), and alloimperatorin methyl ether (8) to allow isolation of relevant carbon atoms in these coumarins. Finally, incorporation studies with DL-mevalonic-5-³ H acid were conducted and subsequent degradative reactions were performed on umbelliprenin (11) and alloimperatorin methyl ether (8). The implications of these preliminary experiments in terms of biosynthetic pathways are presented. / Science, Faculty of / Chemistry, Department of / Graduate

Submitted in partial fulfillment for the Degree of Master of Applied Sciences in Biotechnology, Durban University of Technology, Durban, South Africa, 2016. / Coumarins are naturally occurring α-benzopyrone derivatives known for their pharmacological properties such as anticoagulant, antimicrobial, anticancer, antioxidant, anti-inflammatory and antiviral properties. The pharmacological, biochemical, and curative applications of coumarins depend on the substitution around the coumarin core structure. In the present study, seven halogenated coumarins CMRN1 - CMRN7 were synthesized and evaluated for mosquito larvicidal, repellancy , and insecticidal activity against Anopheles arabiensis. Furthermore, the antimicrobial properties of compounds CMRN1 - CMRN7 were evaluated by assessing the bacterial and fungicidal activities using the disc diffusion method. The anti-inflammatory properties were evaluated using the 5-lipoxygenase kit assay. The evaluation of the safe use of the compounds was determined using the Brine shrimp lethal test. The potential carcinogenic properties of the studied compounds was done using the Salmonella mutagenicity test. The anti-cancer property of the studied compounds was evaluated against UACC62 (Melanoma), MCF-7 (Breast cancer), and PBMC (Peripheral blood mononuclear) cell lines using of MTT assay. The apoptotic potential of the synthesized coumarin was evaluated against UACC62 (Melanoma) cell by assessing their morphological changes, membrane change, mitochondria membrane potential, and caspase-3 activity using the Annexin V-PI staining, JC-1, caspase-3 enzyme kits, respectively, on flow cytometer. The results were compared to a known anti-cancer drug, doxorubicin. The results showed that compounds CMRN1, CMRN2, CMRN4, CMRN5 and CMRN7 exerted 100% larval mortality within 24 h of exposure. All halogenated coumarins reversibly knocked down adult mosquitoes but did not kill them after 24 h of exposure. Furthermore, the adulticidal activity of the compounds was considered only mild to moderate. The antimicrobial activity of the synthetized coumarins CMRN1 - CMRN7 were assessed against E. coli, K. pneumoniae, S. marcescens, S. faecalis, B. cereus, B. coagulans, B. stearothermophilus, C. freundii, S. aureus and M. luteus bacteria and three yeast cultures, C. albicans, C. utilis, S. cerevisiae as well as two fungal species, A. flavus and A. niger. Compounds CMRN1 and CMRN2 showed bacterial growth inhibition for all the tested species except K. pneumonia and B. stearothermophilus. Compounds CMRN4 and CMRN7 showed moderate bacterial inhibition against B. cereus, M. luteus and S. aureus. The anti-inflammatory activity of the coumarins analogues showed that 1 mg/mL of the compounds CMRN1, CMRN2, CMRN4 and CMRN5 displayed moderate anti-inflammatory activity when compared to the positive control, 15-lapoxygenase. The cytotoxicity results of the studied synthetized coumarins displayed selective activity towards the cancer cell lines used in this study. Our studies showed that CMRN1, CMRN2, CMRN4, and CMRN5 had significant cytotoxity effect against UACC-62 (Melanoma) and MCF-7 ( Breast) cancer cells with an inhibitory concentration (IC50) which displayed significant cytotoxicity effect, in particular CMRN4 and CMRN5. These compounds CMRN1- CMRN7 showed no toxicity effect against PBMCs cell line. The mechanism of cell death, that is, necrosis or apoptosis induced by the coumarins was investigated against UACC-62 (Melanoma). We found that CMRN1, CMRN2, CMRN4, CMRN5 induced morphological changes, characteristic of apoptosis . Annexin V kit showed that CMRN1, CMRN2 and CMRN5 showed early apopotosis and late apoptosis was particularly higher for compound CMRN4. The disruption of the mitochondria membrane was noticed to be greater in CMRN1 and CMRN5 when compared to the positive control doxorubicin. Compound CMRN4 produced high levels of caspase-3 positive compared to the control. The coumarin compounds showed no mutagenicity and were also found to be non-toxic to brine shrimps. In conclusion, compounds CMRN1, CMRN2, CMRN4, CMRN5 and CMRN7 are potential larvicidal agents because they exhibited close to 100% activity within 24 h. Furthermore, the anti-cancer efficiency of compounds CMRN1, CMRN2, CMRN4, and CMRN5, is enough qualification for them to be optimized for increase anticancer potency. / M

published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy