Biosynthesis of Natural Products

Natural products are in the form of primary and secondary metabolites and are isolated chemical compounds or substances from living organisms. Terpenes, Phenolic compounds, and Nitrogen-containing compounds are secondary metabolites. The biosyntheses of secondary metabolites are derived from primary metabolism pathways, which consist of a tricarboxylic acid cycle (TCA), methylerythritol phosphate pathway (MEP), mevalonic and shikimic acid pathway. This chapter provides an overview of the diversity of secondary metabolites in plants, their multiple biological functions, and multi-faceted cultural history

Antioxidant and antimicrobial evaluation of the methanol leaf extract and fractions of dacryodes klaineana pierre (burseraceae)

ABSTRACT. Dacryodes klaineana is used in traditional medicine for the treatment of painful menstruation; tachycardia and cough. The study aims to evaluate the antioxidant and antimicrobial properties of the plant. The extract and fractions of D. klaineana were screened for their antioxidant effects using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and the total phenolic contents (TPC) assay methods. The antimicrobial activity of the plant was evaluated using the agar diffusion method against four different bacterialstrains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) and two fungi strains (Aspergillus niger and Candida albicans). The crude methanol extract (MLE), hexane fraction (MLHF), ethyl acetate fraction (MLEF) and butanol fraction (MLBF) produced dose-dependent antioxidant activity using DPPH and FRAP assays. The antioxidant activity of MLEF was comparable to the standard drug, ascorbic acid. MLEF also gave the highest content of total phenol content with a percent gallic acid equivalent of 100.68 ± 1.17 mg GAE/g. The extract and fractions were active against the bacteria species, but inactive against the fungi species. The study demonstrated that the antioxidant and antimicrobial potentials of D. klaineana may offer a promising source of new antioxidants and antimicrobials in the ethnomedicinal management of diseases.                 KEY WORDS: Medicinal plant, FRAP, TPC, DPPH, Antioxidant, Dacryodes klaineana   Bull. Chem. Soc. Ethiop. 2022, 36(1), 85-94.                                                                   DOI: https://dx.doi.org/10.4314/bcse.v36i1.8                                                       &nbsp

Evaluation of Antioxidant, Anti-inflammatory and Antimicrobial Activities of the Leaf Extracts of Luffa cylindrica

Introduction: Luffa cylindrica have been used traditionally in the treatment and management of several disease conditions. This study aimed to evaluate the antioxidant, anti-inflammatory and antimicrobial properties of leaf extracts of the plant, and identifying some of its phytoconstituents. Methods: The crude ethanol and ethyl acetate extracts were evaluated for antioxidant and anti-inflammatory activities using the 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) and paw-fluid displacement methods, respectively. The extracts were tested for antimicrobial activity using the agar well diffusion and agar dilution methods. The ethyl acetate leaf extract of the plant was further subjected to high-performance liquid chromatography-diode-array detection (HPLC-DAD) analysis for the identification of the bioactive compounds. Results: The ethanol and ethyl acetate extracts of L. cylindrica showed average antioxidant properties at 100 µg/mL, with inhibitions of 53.31% and 54.73% respectively. The ethanol extract displayed significant anti-inflammatory activity at 50 mg/Kg with an inhibition of 31.1% compared to 39.7% recorded for the control (diclofenac). The ethyl acetate extract produced an inhibition of 15%. In the antimicrobial evaluation, the ethanol and ethyl acetate extracts showed moderate antibacterial activity against S. aureus, S. Typhi and B. subtilis. The ethyl acetate extract exhibited considerable antimicrobial activity against the test isolates compared to the ethanol extract. HPLC-DAD analysis of the ethyl acetate extract suggested the presence of two flavonoid compounds - luteolin and apigenin as key components of the leaf extract of L. cylindrica. These compounds are known to possess anti-inflammatory, antioxidant and antimicrobial activities. Conclusions: The results of this study showed that the leaf extracts of L. cylindrica possess antioxidant, anti-inflammatory and antimicrobial properties

Antimicrobial Properties and Characterization of Secondary Metabolites Obtained from Curvularia lunata, an Endophyte of Azadirachta indica

Background: Endophyte phytochemicals have piqued interest in drug development programs due to their enormous potential for assisting in the discovery of novel biologically active compounds. Aim and objectives: The study was aimed to isolate, evaluate the antimicrobial properties and characterize the secondary metabolites of Curvularia lunata endophyte isolated from A. indica. Method: C. lunata isolated from A. indica leaves using standard extraction protocols were screened for their potential antimicrobial activities using agar diffusion well method. HPLC-DAD, GC-FID, GC-MS, and FTIR techniques were used to characterize secondary metabolites. Results: At 1 mg/mL, growth inhibition of bacteria by the extracts of C. lunata were observed with Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis, and Candida albicans with zones of inhibition diameters of 6, 5, 4, and 4 mm respectively.  The vacuum liquid chromatography sub-fraction of the extract showed the best antimicrobial activity. HPLC-DAD analysis revealed the presence of 2-carboxymethyl-3-n-hexylmaleic acid anhydride and aspernigin A. GC-FID analysis showed remarkably high concentrations of flavonones and catechins. The results of GC-MS analysis also showed the presence of hexadecanoic acid, and 1,6-Anhydro-beta-D-glucopyranose. FTIR results established the presence of functional groups like carboxylic acids, which may be associated with some of the detected compounds. Conclusion: C. lunata (OM337582) extract of A. indica have potent antimicrobial activity which could be related to a high content of flavonoids and alkaloids. Keywords: Antimicrobial, Azadirachta indica, HPLC-DAD, Chromatography, Curvularia lunata

New amide and dioxopiperazine derivatives from leaves of Breynia nivosa

The first chemical investigation of leaves of Breynia nivosa from Nigeria resulted in the isolation of two new amide derivatives breynivosamides A and B (1 and 2) and two new dioxopiperazine derivatives breynivosines A and B (4 and 5) together with seven known compounds (3, 6–11). The structures of the new compounds were elucidated by 1D, 2D NMR and HRESIMS data as well as by comparison with the literature. All isolated compounds were tested for the cytotoxic and antimicrobial activities. Only cristatin A (6) showed cytotoxicity against the L5178Y mouse lymphoma cell line with an IC50 value of 13.9 μM while breynivosamide A (1) exhibited moderate antimicrobial activity against Mycobacterium tuberculosis with an MIC value of 25 μM

The ASOS Surgical Risk Calculator: development and validation of a tool for identifying African surgical patients at risk of severe postoperative complications

Background: The African Surgical Outcomes Study (ASOS) showed that surgical patients in Africa have a mortality twice the global average. Existing risk assessment tools are not valid for use in this population because the pattern of risk for poor outcomes differs from high-income countries. The objective of this study was to derive and validate a simple, preoperative risk stratification tool to identify African surgical patients at risk for in-hospital postoperative mortality and severe complications. Methods: ASOS was a 7-day prospective cohort study of adult patients undergoing surgery in Africa. The ASOS Surgical Risk Calculator was constructed with a multivariable logistic regression model for the outcome of in-hospital mortality and severe postoperative complications. The following preoperative risk factors were entered into the model; age, sex, smoking status, ASA physical status, preoperative chronic comorbid conditions, indication for surgery, urgency, severity, and type of surgery. Results: The model was derived from 8799 patients from 168 African hospitals. The composite outcome of severe postoperative complications and death occurred in 423/8799 (4.8%) patients. The ASOS Surgical Risk Calculator includes the following risk factors: age, ASA physical status, indication for surgery, urgency, severity, and type of surgery. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.805 and good calibration with c-statistic corrected for optimism of 0.784. Conclusions: This simple preoperative risk calculator could be used to identify high-risk surgical patients in African hospitals and facilitate increased postoperative surveillance. © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.Medical Research Council of South Africa gran

Maternal and neonatal outcomes after caesarean delivery in the African Surgical Outcomes Study: a 7-day prospective observational cohort study.

BACKGROUND: Maternal and neonatal mortality is high in Africa, but few large, prospective studies have been done to investigate the risk factors associated with these poor maternal and neonatal outcomes. METHODS: A 7-day, international, prospective, observational cohort study was done in patients having caesarean delivery in 183 hospitals across 22 countries in Africa. The inclusion criteria were all consecutive patients (aged ≥18 years) admitted to participating centres having elective and non-elective caesarean delivery during the 7-day study cohort period. To ensure a representative sample, each hospital had to provide data for 90% of the eligible patients during the recruitment week. The primary outcome was in-hospital maternal mortality and complications, which were assessed by local investigators. The study was registered on the South African National Health Research Database, number KZ_2015RP7_22, and on ClinicalTrials.gov, number NCT03044899. FINDINGS: Between February, 2016, and May, 2016, 3792 patients were recruited from hospitals across Africa. 3685 were included in the postoperative complications analysis (107 missing data) and 3684 were included in the maternal mortality analysis (108 missing data). These hospitals had a combined number of specialist surgeons, obstetricians, and anaesthetists totalling 0·7 per 100 000 population (IQR 0·2-2·0). Maternal mortality was 20 (0·5%) of 3684 patients (95% CI 0·3-0·8). Complications occurred in 633 (17·4%) of 3636 mothers (16·2-18·6), which were predominantly severe intraoperative and postoperative bleeding (136 [3·8%] of 3612 mothers). Maternal mortality was independently associated with a preoperative presentation of placenta praevia, placental abruption, ruptured uterus, antepartum haemorrhage (odds ratio 4·47 [95% CI 1·46-13·65]), and perioperative severe obstetric haemorrhage (5·87 [1·99-17·34]) or anaesthesia complications (11·47 (1·20-109·20]). Neonatal mortality was 153 (4·4%) of 3506 infants (95% CI 3·7-5·0). INTERPRETATION: Maternal mortality after caesarean delivery in Africa is 50 times higher than that of high-income countries and is driven by peripartum haemorrhage and anaesthesia complications. Neonatal mortality is double the global average. Early identification and appropriate management of mothers at risk of peripartum haemorrhage might improve maternal and neonatal outcomes in Africa. FUNDING: Medical Research Council of South Africa.Medical Research Council of South Africa