http://hdl.handle.net/123456789/90 Sun, 19 Apr 2026 01:43:05 GMT 2026-04-19T01:43:05Z http://hdl.handle.net/123456789/2123 BIOASSAY-GUIDED ISOLATION, CHARACTERISATION AND CYTOTOXICITY OF MOSQUITO REPELLENT COMPOUNDS FROM SELECTED MEDICINAL PLANTS ADENIYI-AKEE, MUKARAM AKINTUNDE Malaria, a tropical disease caused by Plasmodium parasites and spread by the bites of infected female Anopheles mosquitoes, remains a major public health issue. Mosquito repellents are used as a control measure.Existing synthetic repellents present challengesof high insecticide resistance, allergic reactions, and non-biodegradable residues. This has necessitated the search for alternative repellent compounds from natural sources.This study was designed to evaluate the repellent activity of selected ethnomedicinal plants against wild adult female Anopheles gambiae (s.l.), and characterise isolated bioactive compounds. Dry powdered plant parts of Citrus limon Linn. (seeds), Citrus paradisi Macf. (seeds), Citrus sinensisL.(seeds), Jatropha curcas L.(seeds), Dennettia tripetala G. (fruits), and Afromomum melegueta K. (fruits) were successively extracted with n-hexane (Hex), ethyl acetate (EA) and methanol by cold maceration. Phytochemical screening of the extracts was done using standard methods. The extracts were screened against A. gambiae for their repellent activity using human bait method, whileN,N-diethyl-meta-toluamide(DEET) and acetone were used as positive and negative controls, respectively. Extracts with the highest percentage repellency, calculated using standard formula, were subjected to bioassay-guided fractionation and separation using chromatographic techniques. Isolated compounds were evaluated for cytotoxicity using brine shrimp lethality assay (safety cutoff, LC50> 100µg/mL), and characterised by spectroscopic (IR, 1D and 2D NMR) and mass spectrometric analyses. Repellent activity data were analysed using one-way ANOVA at α0.05. Extraction of the plant materials yielded eighteen extracts. Phytochemical screening of the extracts revealed the presence of alkaloids, flavonoids, tannins, glycoside, saponins, and anthraquinones. The screened extracts, tested at 1.5, 2.5, and 5mg/mL, gave percentage repellency of ≤ 68.1, ≤ 74.9, and ≤ 97.5%, respectively (DEET, 100%). At 5 mg/mL, the percentage repellency of the three most active extracts (C. limon (Hex, 97.5%), D. tripetala (EA, 87.7%), and C. limon (methanol, 86.8%) were not significantly different (α˂0.05). Citrus limon (Hex) fractionation yielded 10 fractions with percentage repellency of ≤ 89.5 %, whileD. tripetala (EA) yielded eleven fractions which were pooled into four (DTH1, 55.7%; DTH2, 60.6%; DTEA, 77.2%, and DTM, 71.1%). n-Hexane-100% and Hex/EA (9:1) fractions of C. limon, DTEA and DTM fractions of D. tripetala showed the most repellency effects of 89.5%, 71.1%, 77.2% and 71.1%, respectively. Chromatographic purification of n-hexane-100%, Hex/EA (9:1) and DTEA gave seven compounds. They were identified as palmitic acid (a), 14-oxotricosanoic acid (b),n-octyl stearate(c), 15-(heptanoyloxy) pentadec-9-enoic acid (d), 6,8-dimethoxy-3-undecyl-1H- [2]benzopyran-1-one (e), 1,2,3-propanetriyl tris(5-eicosenoate) (f), and α-linoleic acid (g) with percentage repellency of 65.9, 63.6, 51.7, 77.9, 75.2, 37.0, and 57.3%, respectively. Cytotoxicity evaluation of compounds a-e gaveLC50ranging from 63.2 to 171.1 µg/mL, with compounds c (106.1 µg/mL) and e (171.1 µg/mL) being adjudged safe. Compoundd showed the highest repellent activity against A. gambiae mosquito. Extracts of Citrus limon and Dennettia tripetalacontain potentially useful mosquito repellent compounds. n-Octyl stearate and 6,8-dimethoxy-3-undecyl-1H-[2]benzopyran-1- one (both from C. limon) may serve as leads for the development of novel bio-degradable and safe mosquito repellent compounds. Sun, 01 Jan 2023 00:00:00 GMT http://hdl.handle.net/123456789/2123 2023-01-01T00:00:00Z http://hdl.handle.net/123456789/1074 BIOACTIVITY-GUIDED ISOLATION AND STRUCTURE ELUCIDATION OF ANTIMALARIAL TRITERPENES FROM Combretum zenkeriENGL & DIELS AND Combretum racemosumP. BEAUV. LEAVES OLUYEMI, Wande Michael Medicinal plants are rich sources of antimalarial compounds. Combretaceae family is known from ethnobotanical survey to possess broad spectrum of activities against different diseases including malaria. The increasing trend of resistance to many antimalarial agents including artemisinin and its derivatives has necessitated the need for new drug candidates. This study was, therefore, designed to validate the antimalarial potential of selected Combretaceae species, investigate the most active plant extracts by bioactivity-guided isolation and structure elucidation of the active principles. Methanol and acetone extracts of the leaves of ten Combretaceae species, collected from the University of Ibadan Botanical Garden, were obtained by Soxhlet method. These extracts were screened for inhibition of β-hematin synthesis monitored with UV-Visible spectrophotometer at 405 nm. The most active methanol extracts, Combretum racemosum (CRM) [FHI/108887] and Combretum zenkeri (CZM) [FHI/110277] were screened against chloroquine-sensitive D10 and chloroquine-resistant W2 Plasmodium falciparum strains using lactate dehydrogenase assay with chloroquine as the standard. Both extracts were successively partitioned into chloroform and n-butanol by solvent-solvent partitioning, fractions obtained were also investigated for anti-plasmodial activity. The chloroform fractions were subjected to flash and column chromatographic techniques for bioactive compound isolation. Isolated compounds were characterised by NMR and MS techniques (1D and 2D NMR, ESI-MS and HR-ESIMS) and subjected to anti-plasmodial screening. Structure-activity relationship (SAR) study of the isolated compounds was conducted. The IC50 was calculated by curve-fitting analysis. Statistical analyses were conducted using a two-tailed Student’s t test at α0.05. The CZM (IC50: 2.92±0.846 mg/mL) and CRM (IC50: 3.96±0.132 mg/mL) crude extracts had significant activities. The CRM [D10: IC50= 64.18±2.69 µg/mL (R2 = 0.99); W2: IC50= 65.80±14.85 µg/mL (R2 = 0.96)] and CZM [D10: IC50= 68.98±1.00 µg/mL (R2 = 0.95); W2: IC50= 69.68±3.09 µg/mL (R2 = 0.99)] crude extracts showed antiplasmodial activity. The CRM chloroform fraction (D10: IC50= 33.80±1.52 µg/mL; W2: IC50= 27.82±2.85 µg/mL) showed higher activity relative to the n-butanol fraction (D10: IC50= 78.08±7.29 µg/mL; W2: IC50= 78.12±14.98 µg/mL). The chloroform fraction of CZM (D10: IC50= 12.57±1.57 µg/mL; W2: IC50= 12.14±0.95 µg/mL); also had higher activity than n-butanol fraction (D10: IC50= 61.98±3.25 µg/mL; W2: IC50= 61.26±8.64 µg/mL). Phytochemical isolation from the C. racemosum chloroform fraction led to the identification of four ursane-type triterpenes: 19α-hydroxyasiatic acid, 6β, 23-dihydroxytormentic acid, madecassic acid, nigaichigoside F1; four oleanane-type triterpenes: arjungenin, combregenin, terminolic acid, arjunglucoside I, and abscisic acid. All isolated compounds exhibited antiplasmodial activity (17.19±4.34 ≤ IC50 ≤ 134.70±13.21 µg/mL) with madecassic acid showing significant activity [D10: IC50= 27.62±11.56 µg/mL (R2 = 0.96); W2: IC50= 17.19±4.34 µg/mL (R2 = 0.98)]; however, chloroquine standard showed higher activity (D10: IC50= 0.01±0.002 µg/mL; W2: IC50= 0.22±0.03 µg/mL) than madecasic acid. The chloroform fraction of C. zenkeri led to the isolation of two triterpenes, ursolic and oleanolic acids, with known antimalarial activities. The SAR showed that dehydroxylation at 6β- and/or 19α-positions in these triterpenes increased the antiplasmodial activity, while the geminal-dimethyl substitutions at position C-20 did not significantly impact the bioactivity. The antiplasmodial potential of Combretum racemosum and Combretum zenkeri was validated. Madecassic acid showed potential for antimalarial drug development. Sat, 01 Feb 2020 00:00:00 GMT http://hdl.handle.net/123456789/1074 2020-02-01T00:00:00Z