Quinone Derivatives as Promising Anti-Helicobacter pylori Agents from Aerial Parts of Mitracarpus hirtus.

Seven new naphthoquinone diglycosides (1-7), three new anthraquinones (8-10), and eight known analogues were obtained from the aerial parts of Mitracarpus hirtus collected from West Africa in a bioassay-guided phytochemical investigation. All isolated compounds were elucidated by comparison with the literature and interpretation of spectroscopic data, and the absolute configurations of the new naphthoquinone diglycosides (1-10) were confirmed by chemical methods and ECD calculations. Notably, compound 1 was found to be the first naphthoquinone diglycoside containing carboxylic acid and isopentenyl side chains isolated from a species in the genus Mitracarpus. Compounds 6-18 showed antibacterial activity against multiple Helicobacter pylori strains with MIC values ranging from 0.0625 to 64 µg/mL. Particularly, 1-hydroxybenzoisochromanquinone (17) and benzo[g]isoquinoline-5,10-dione (18), with MIC values of 0.0625 and 0.125 µg/mL, displayed 32-512-fold higher potencies than a positive control, metronidazole. Compound 18 also demonstrated high antibiofilm activity and killed biofilm-encased Helicobacter pylori cells more effectively than metronidazole.

(9ßH)- and 17-Nor-Pimaranes from Icacina oliviformis.

Eleven pimarane-type diterpenoids were isolated from the tubers of Icacina oliviformis, including three new compounds, icacinlactone M (9), icacinlactone H 2-O-ß-d-glucopyranoside (10), and icacinlactone N 3-O-ß-d-glucopyranoside (11), together with an artifact of acrenol (8). Among the known structures, icacinlactone A (2), icacinlactone B (3), icacinlactone H (4), 12-hydroxyicacinlactone A (5), 14α-methoxyhumirianthol (6), and annonalide (7) are reported from I. oliviformis for the first time, whereas icacinol (1) has previously been found in this plant. Icacinol, 14α-methoxyhumirianthol, and annonalide displayed moderate cytotoxic activity in a panel of human cancer cell lines.

Di-nor- and 17-nor-pimaranes from Icacina trichantha.

Six new pimarane derivatives, including two di-nor-pimaranes (1, 2), two 17-nor-pimaranes (3, 4), and two 17-nor-(9ß-H)-pimaranes (5, 6), were isolated from the tuber of Icacina trichantha. Their structures were elucidated based on spectroscopic and HRMS data. The absolute configurations of 1 and 5 were determined by single-crystal X-ray diffraction, and that of 2 was established by electronic circular dichroism data analysis. Compound 3 possesses a unique C-20 acetal moiety. This is the first report of the isolation of di-nor-(9ß-H)-pimarane derivatives from Icacina plants. Compounds 5 and 6 showed moderate cytotoxicity against MDA-MB-435, MDA-MB-231, and OVCAR3 cell lines, with IC50 values of 2.91-7.60 and 1.48-3.23 µM, respectively.

(9ßH)-Pimaranes and Derivatives from the Tuber of Icacina trichantha.

New 17-nor-pimaranes (1, 2), (9ßH)-pimaranes (3, 4), and 17-nor-(9ßH)-pimarane (5) were isolated from the tuber of Icacina trichantha. The structures were elucidated based on spectroscopic and HRMS data. The absolute configurations of 3 and 5 were determined by single-crystal X-ray diffraction. Compound 5 possesses a unique 19,20-δ-lactone moiety. Compound 3 showed cytotoxicity against MDA-MB-435 (human melanoma cancer) cells with an IC50 value of 7.04 µM. A plausible biogenetic pathway for compounds 1-5 is proposed.

Chemical constituents of the aerial parts of Mitracarpus hirtus (L.) DC (Rubiaceae).

A phytochemical investigation of the aerial parts of Mitracarpus hirtus afforded thirteen compounds, including a new naphthoquinone di-glycoside (1), three isopentenyl isoflavones (2-4), four flavonoids (5-8), three iridoid glycosides (9 - 11) and two coumarins (12 and 13). Their structures were elucidated based on extensive spectroscopic analyses, chemical methods, and the comparison with the literature. Among them, compound 1 possesses a 2-(3-methylnaphthalen-2-yl)acetic acid core with two glucosyl groups, compounds 2-4 are the first three representatives from the Rubiaceae family, and compounds 9-11 and 13 were isolated from Mitracarpus genus for the first time. Additionally, compounds 2-4 displayed potent antibacterial activities against Helicobacter pylori G27/HP159/JRES00015 (MIC = 4-16 µg/mL) , comparable to metronidazole. To date, wighteone (2) is the most active isoflavone with favourable predicted ADMET properties reported against H. pylori.

Structurally diverse (9ß-H)-pimarane derivatives with six frameworks from the leaves of Icacina oliviformis and their cytotoxic activities.

Thirteen previously undescribed (9ß-H)-pimarane derivatives, icacinolides A-G (1-7) and oliviformislactones C-H (8-13), together with four known analogs (14-17), were isolated from the leaves of Icacina oliviformis. Their structures were constructed by extensive spectroscopic analysis, 13C NMR-DP4+ analysis, ECD calculation, single-crystal X-ray diffraction, and chemical methods. These structurally diverse isolates were classified into six framework types: rearranged 3-epi-17-nor-(9ß-H)-pimarane, rearranged 17-nor-(9ß-H)-pimarane, 16-nor-(9ß-H)-pimarane, 17-nor-(9ß-H)-pimarane, 17,19-di-nor-(9ß-H)-pimarane, and (9ß-H)-pimarane. Among them, compounds 1, 5, and 7 were the first examples of three rearranged 3-epi-17-nor-(9ß-H)-pimaranes featuring a unique (11S)-carboxyl-9-oxatricyclo[5.3.1.02,7]dodecane motif with contiguous stereogenic centers, whereas their C-3 epimers, compounds 2-4 and 6 were the second examples of four rearranged 17-nor-(9ß-H)-pimaranes. Additionally, compounds 8 and 12/13 represented the second examples of a 16-nor-(9ß-H)-pimarane and two 17,19-di-nor-(9ß-H)-pimaranes, respectively. In cytotoxic bioassay, compound 2 exhibited significant cytotoxic against HT-29 with IC50 values of 7.88 µM, even stronger than 5-fluorouracil, and 15 showed broad-spectrum cytotoxic activities against HepG2, HT-29, and MIA PaCa-2 with IC50 values of 11.62, 9.77, and 4.91 µM, respectively. Meanwhile, a preliminary structure-activity relationship suggested that 3,20-epoxy, 6,19-lactone, 2-OH, 7-OH, and 8-OH in (9ß-H)-pimarane derivatives might be active groups, whereas ring C aromatization may decrease the cytotoxic activities.

19-nor-pimaranes from Icacina trichantha.

Four new unusual 19-nor-pimarane-type diterpenes were isolated from the tuber of Icacina trichantha (Icacinaceae, Oliv.). The structures were elucidated based on spectroscopic and HRMS analysis. The absolute configurations were determined by electronic circular dichroism. All four compounds are structural analogues of icacinol and humirianthol, but do not demonstrate the same cytotoxic activity. A plausible biogenetic pathway is proposed.

Knowledge, Attitudes, and Perceptions Associated With Antimicrobial Stewardship Among Veterinary Students: A Multi-Country Survey From Nigeria, South Africa, and Sudan.

In African countries, antimicrobial resistance (AMR) issue remains pertinent. Despite this, little efforts have been made to assess the future veterinary prescribers on their knowledge, attitudes and practices (KAP) related to antimicrobial usage. This multi-country survey attempts to explore the KAP of future veterinarians on stewardship of antimicrobial and identify knowledge gaps. Eight veterinary schools participated from Nigeria, Sudan and South Africa. Data regarding perceptions and knowledge were analyzed using Chi-square χ2 test, Spearman's (Rho) Rank order correlation and factor analysis using principal component factoring extraction method. Fifty-two percent of the study participants were final year veterinary students, respectively, and majority (77.2%) had no previous knowledge of biomedical sciences. Majority age were 22-27 years (24.7 ± 2.8) 79% and multiple career fields post-graduation were preferred. Overall, poor perceptions and knowledge of antimicrobial stewardship were observed with variations among countries and only 36.3% (n = 123) of the students were confident in their ability to choose the ideal antimicrobial agents for a specific patient/group of animals. The majority of the final year students were confident of their knowledge regarding AMR (68%), making of Gram staining (69.2%) and in choosing the most ideal route for administering a specific antimicrobial (74.7%). The final year students had significantly (p < 0.05) higher confidence level for knowledge compared with the pre-final year students. Tetracyclines, penicillins, and sulphonamides represent the three most abused veterinary antimicrobials with similar ranking across countries. South African (69.7 ± 20.5) and Sudanese (68.1 ± 15.4) had significantly (p < 0.0001) higher mean scores compared to the Nigerian students (44.3 ± 6.8) in the student's ability to correctly match some specific antimicrobials against their classes but Nigerian students performed better in ranking antimicrobials. This survey revealed poor to average knowledge of antimicrobial stewardship among veterinary students with significant knowledge gaps across the countries. It is recommended that the relevant regulatory and standardization authorities should make concerted efforts and interventions to regularly review curricula to ensure the delivery of targeted formative and normative training, and improved lectures on antimicrobial usage and stewardship in order to improve the awareness and behaviors of future prescribers. The identified knowledge gaps of veterinary medical students on antimicrobial stewardship must be bridge to safeguard the future.

Icacinlactone H and Icacintrichantholide from the Tuber of Icacina trichantha.

The 17-norpimarane diterpene is a small group of natural products. A new member, icacinlactone H (1), and a new rearranged 17-norpimarane with an unprecedented carbon skeleton, icacintrichantholide (2), were isolated from Icacina trichantha. Their structures including the absolute configuration were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism analysis. A plausible biogenetic pathway for 1 and 2 is proposed. Both 1 and 2 showed no significant activity against herpes simplex viruses HSV-1 and HSV-2 as well as the Epstein-Barr virus at 50 µM.