Abiodun Oguntuga Ogundaini

Antimicrobial constituents of the leaves of Acalypha wilkesiana and Acalypha hispida

An Erratum for this article has been published in Phytotherapy Research 14(8), 2000, 661.

Doubly linked, A-type proanthocyanidin trimer and other constituents of Ixora coccinea leaves and their antioxidant and antibacterial properties

Phytochemical investigation of the ethyl acetate fraction of the methanol extract of the leaves of Ixora coccinea led to the isolation and identification of an A-type trimeric proanthocyanidin epicatechin-(2β→O→7, 4β→8)-epicatechin-(5→O→2β, 6→4β)-epicatechin named ixoratannin A-2 along with seven known compounds, epicatechin, procyanidin A2, cinnamtannin B-1, and four flavon-3-ol rhamnosides viz: kaempferol-7-O-α-L-rhamnnoside, kaempferol-3-O-α-L-rhamnoside, quercetin-3-O-α-L-rhamnopyranoside, and kaempferol-3,7-O-α-L-dirhamnoside. The structures were elucidated by the application of IR, UV, MS, 1D-, and 2D-NMR spectroscopic analyses and by comparison with literature data. Antioxidant evaluation of isolated compounds revealed that ixoratannin A-2 and cinnamtannin B-1 were the most active compounds in DPPH, inhibition of lipid peroxidation and nitric oxide radical scavenging assays. Antibacterial activities were assessed by means of agar-diffusion assays using Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis. All tested compounds inhibited the growth of B. subtilis, while only epicatechin and quercetin-3-O-α-L-rhamnopyranoside inhibited the growth of E. coli.

Antimicrobial Spectrum of Alchornea cordifolia Leaf Extract

The 50% aqueous ethanol extract of Alchornea cordifolia (Schum and Thonn) Muell. Arg. leaf was screened for activity against 74 microbial strains representing aerobic, facultative and anaerobic bacteria as well as fungi. The panel of test strains included organisms from culture collections as well as clinical and environmental isolates. A concentration of 5 mg/mL of extract inhibited 36.5% of the isolates and 95.9% were inhibited by a concentration of 20 mg/mL. Only three strains, all filamentous fungi, were not susceptible to 40 mg/mL of the extract, the highest concentration tested. The extract showed the best activity against gram‐positive bacteria and yeasts with inhibitory concentrations against these organisms being under 5 mg/mL. The results demonstrate that the A. cordifolia extract has a very broad spectrum of activity and suggests that it may be useful in the treatment of various microbial infections. Copyright

Piliostigmin, A 2-phenoxychromone, and C-methylflavonols from Piliostigma thonningii

Abstract Piliostigmin, a 2-phenoxychromone, and three C -methylflavonols, 6,8-di- C -methylquercetin 3-methyl ether, 6- C -methylquercetin 3,7-dimethyl ether and 6,8-di- C -methylquercetin 3,7-dimethyl ether, were isolated from the leaves of Piliostigma thonningii , together with the known compounds quercetin, quercitrin, 6- C -methylquercetin 3-methyl ether, 6- C -methylquercetin 3,7,3′-trimethyl ether, 6,8-di- C -methylkaempferol 3-methyl ether and 6,8-di- C -methylkaempferol 3,7-dimethyl ether. The structures of the new compounds were established by spectral methods, especially 2D NMR. Complete 13 C assignments using HMBC experiments are reported for the four latter C -methylflavonols.

Antiinflammatory and antibacterial activities of C-methylflavonols from Piliostigma thonningii

Newly described C‐methylflavonols, 6,8‐di‐C‐methylquercetin 3‐methyl ether, 6‐C‐methylquercetin 3,7‐dimethyl ether, 6,8‐di‐C‐methylquercetin 3,7‐dimethyl ether together with the known compounds quercetin, quercitrin, 6‐C‐methylquercetin 3‐methyl ether, 6‐C‐methylquercetin 3,7,3′‐trimethyl ether, 6,8‐di‐C‐methyl‐ kaempferol 3‐methyl ether and 6,8‐di‐C‐methylkaempferol 3,7‐dimethyl ether isolated from the leaves of Piliostigma thonningii, were tested for their ability to inhibit prostaglandin synthesis in vitro and antibacterial activity against Staph. aureus. The influence of the B ring 3′,4′ diol group on the activity of C‐methylflavonols in the inhibition of prostaglandin synthesis differ from that observed for a series of flavonoids without C‐methyl groups. The antibacterial activity in the series mirror those of methylated antimicrobial flavonoids. The traditional uses of the plant in infections and inflammatory conditions were rationalized on the basis of the activities of these compounds.

Virtualizing the p-ANAPL Library: A Step towards Drug Discovery from African Medicinal Plants

Background Natural products play a key role in drug discovery programs, both serving as drugs and as templates for the synthesis of drugs, even though the quantities and availabilities of samples for screening are often limitted. Experimental approach A current collection of physical samples of > 500 compound derived from African medicinal plants aimed at screening for drug discovery has been made by donations from several researchers from across the continent to be directly available for drug discovery programs. A virtual library of 3D structures of compounds has been generated and Lipinski’s “Rule of Five” has been used to evaluate likely oral availability of the samples. Results A majority of the compound samples are made of flavonoids and about two thirds (2/3) are compliant to the “Rule of Five”. The pharmacological profiles of thirty six (36) selected compounds in the collection have been discussed. Conclusions and implications The p-ANAPL library is the largest physical collection of natural products derived from African medicinal plants directly available for screening purposes. The virtual library is also available and could be employed in virtual screening campaigns.

Screening of the pan-African Natural Product Library identifies ixoratannin A-2 and boldine as novel HIV-1 inhibitors

The continued burden of HIV in resource-limited regions such as parts of sub-Saharan Africa, combined with adverse effects and potential risks of resistance to existing antiretroviral therapies, emphasize the need to identify new HIV inhibitors. Here we performed a virtual screen of molecules from the pan-African Natural Product Library, the largest collection of medicinal plant-derived pure compounds on the African continent. We identified eight molecules with structural similarity to reported interactors of Vpu, an HIV-1 accessory protein with reported ion channel activity. Using in vitro HIV-1 replication assays with a CD4+ T cell line and peripheral blood mononuclear cells, we confirmed antiviral activity and minimal cytotoxicity for two compounds, ixoratannin A-2 and boldine. Notably, ixoratannin A-2 retained inhibitory activity against recombinant HIV-1 strains encoding patient-derived mutations that confer resistance to protease, non-nucleoside reverse transcriptase, or integrase inhibitors. Moreover, ixoratannin A-2 was less effective at inhibiting replication of HIV-1 lacking Vpu, supporting this protein as a possible direct or indirect target. In contrast, boldine was less effective against a protease inhibitor-resistant HIV-1 strain. Both ixoratannin A-2 and boldine also inhibited in vitro replication of hepatitis C virus (HCV). However, BIT-225, a previously-reported Vpu inhibitor, demonstrated antiviral activity but also cytotoxicity in HIV-1 and HCV replication assays. Our work identifies pure compounds derived from African plants with potential novel activities against viruses that disproportionately afflict resource-limited regions of the world.

Complete1H and13C NMR assignment of a kaurane diterpene fromPiliostigma thonningii

The diterpene ent‐16α‐hydroxykauran‐18‐oic acid was isolated from the leaves of Piliostigma thonningii. Structural elucidation and complete 1H and 13C NMR chemical shift assignments of this compound were achieved by 2D experiments.

ISOLATION AND CHARACTERIZATION OF CHEMICAL CONSTITUENTS FROM CHRYSOPHYLLUM ALBIDUM G. DON-HOLL. STEM-BARK EXTRACTS AND THEIR ANTIOXIDANT AND ANTIBACTERIAL PROPERTIES.

Background: The plant, Chrysophyllum albidum is indigenous to Nigeria and its stem-bark has wide application in traditional medicine for the treatment of infections and oxidative stress related diseases. The aim of the study was to isolate the chemical constituents responsible for the antioxidant and antibacterial activity from the stem-bark of the plant in order to justify some of its ethnomedicinal uses. Materials and Methods: Crude extract of stem-bark of Chrysophyllum albidum obtained from 80% ethanol was successively partitioned with ethyl acetate (EtOAc) and n-butanol. The solvent fractions and isolated compounds were tested for antioxidant property using 2-2-diphenyl-1-picrylhydrazyl. Antibacterial activities were also assessed by means of agar-diffusion and broth micro dilution methods. EtOAc fraction was repeatedly fractionated on column chromatography to afford four compounds and their chemical structures were established using NMR (1D and 2D) and MS. Results: Chromatographic fractionation of EtOAc fraction with the highest antioxidant and antimicrobial activities afforded stigmasterol (1),: epicatechin (2),: epigallocatechin (3): and procyanidin B5 (4).: Procyanidin B5 isolated for the first time from genus Chrysophyllum demonstrated the highest antioxidant activity with IC50 values of 8.8 μM and 11.20 μM in DPPH and nitric oxide assays respectively and equally demonstrated the highest inhibitory activity against Escherichia coli (MIC 156.25 μg/mL), Staphylococcus aureus (MIC 156.25 μg/mL), Pseudomonas aeruginosa (MIC 625 μg/mL) and Bacillus subtilis (MIC 156.25 μg/mL). Conclusion: The antibacterial and antioxidant activities of epicatechin, epigallocatechin and procyanidin B5 isolated from Chrysophyllum albidum stem-bark validate the folkloric uses.

Antimicrobial activity of eleagnine isolated from the seed cotyledons of Chrysophyllum albidum

This study evaluated the antimicrobial activity of eleagnine, a β -carboline alkaloid isolated from seed cotyledons of Chrysophyllum albidum G. Don Holl (Sapotaceae), and determined factors affecting it. Antimicrobial activities of eleagnine were determined using the agar diffusion and microdilution methods against selected typed organisms ( Bacillus subtilis , Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa , Candida spp.), clinical isolates ( S. aureus , E. coli ) and Trichophyton. The effects of inoculum size and pH on the bacteriostatic activity were studied using agar and broth dilution methods. Bactericidal/fungicidal activities were also evaluated using viable count technique. Cytotoxicity was determined using brine shrimp lethality test. Eleagnine showed higher bacteriostatic activity against Gram-positive organisms and Candida spp. than Gram-negative bacteria but showed no activity against Trichophyton. The MIC of eleagnine obtained by microdilution tests ranged from 9.77 μ g/mL against S. aureus , 156.25 μ g/mL for C. albicans to 312.5 μ g/mL for E. coli and P. aeruginosa . Inoculum size (10 5 -10 7 orgs/mL) did not appreciably affect activity but pH from 5.85 to 8.09 increased the activity against S. aureus and E. coli , suggesting the unionized form as the active compound. Eleagnine (100-400 μ g/mL) produced a 4-5 log survivor reduction of S. aureus and E. coli in 30 min. LC 50 of eleagnine was 18.8 mg/mL indicating minimal cytotoxicity. This study showed that eleagnine is bactericidal with low cytotoxicity. Factors affecting its activity (pH, solvent) could be optimized in developing effective antimicrobial products alone or in combination with other agents. Keywords: Eleagnine, Chrysophyllum albidum , antimicrobial, inoculum size, pH