Acid 1a Research Articles

Synthesis and antiviral activity of fatty acyl conjugates of remdesivir against severe acute respiratory syndrome coronavirus 2 and Ebola virus

We report here the synthesis, purification, and characterization of mono- and di-fatty acyl conjugates of remdesivir (RDV) and their in vitro antiviral activity against SAR-CoV-2, an Ebola virus transcription- and replication-competent virus-like particle (trVLP) system, and infectious Ebola virus. The most potent monofatty acyl conjugate was 4b, containing a 4-oxatetradecanolyl at the 3′ position. Monofatty acyl conjugates, 3′-O-tetradecanoyl (4a) (IC50(VeroE6) = 2.3 μM; IC50(Calu3) = 0.24 μM), 3′-O-4-oxatetradodecanoyl (4b) (IC50(VeroE6) = 2.0 μM; IC50(Calu3) = 0.18 μM), and 3′-O-(12-ethylthiododecanoyl) (4e) (IC50(VeroE6) = 2.4 μM; IC50(Calu3) = 0.25 μM) derivatives exhibited less activity than RDV (IC50(VeroE6) = 0.85 μM; IC50(Calu3) = 0.06 μM) in both VeroE6 and Calu3 cells. Difatty acylation led to a significant reduction in the antiviral activity of RDV (as shown in conjugates 5a and 5b) against SARS-CoV-2 when compared with monofatty acylation (3a-e and 4a-e). About 77.9% of 4c remained intact after 4 h incubation with human plasma while only 47% of parent RDV was observed at the 2 h time point. The results clearly indicate the effectiveness of fatty acylation to improve the half-life of RDV. The antiviral activities of a number of monofatty acyl conjugates of RDV, such as 3b, 3e, and 4b, were comparable with RDV against the Ebola trVLP system. Meanwhile, the corresponding physical mixtures of RDV and fatty acids 6a and 6b showed 1.6 to 2.2 times less antiviral activity than the corresponding conjugates, 4a and 4c, respectively, against SARS-CoV-2 in VeroE6 cells. A significant reduction in viral RNA synthesis was observed for selected compounds 3a and 4b consistent with the IC50 results. These studies indicate the potential of these compounds as long-acting antiviral agents or prodrugs of RDV.

Design, Synthesis, and Biological Evaluation of Hybrid Glypromate Analogues Using 2-Azanorbornane as a Prolyl and Pipecolyl Surrogate.

Neurodegenerative disorders of the central nervous system are a class of heterogeneous pathologies affecting millions of people worldwide and represent a global health burden in developed and developing countries. Without restorative treatments currently available, research on neuroprotective drugs is considered a health priority. In this study, new analogues of the glycyl-l-prolyl-l-glutamic acid (Glypromate) neuropeptide were designed, synthesized, and biologically evaluated using (1R,3S,4S)-2-azanorbornane-3-carboxylic acid as a hybrid construct of l-proline and l-pipecolic acid. Neuroprotection assays carried out in human neuroblastoma SH-SY5Y cells using 6-hydroxydopamine as a stress inducer showed great percentage of recovery (29.7-40.0%) at 100 μM. Among this series, [(1R,3S,4S)-2-glycyl-2-azanorbornane-3-carbonyl]-l-aspartic acid (2a) stands out with a remarkable percentage of recovery (40.0%, at 100 μM) and safe toxicological profile in SH-SY5Y and human adipose mesenchymal stem cells.

Effects of an alternating linseed oil-fish oil feeding strategy on growth, fatty acid restoration and expression of lipid related genes in black seabream (A. schlegelii)

An eight-week feeding trial was conducted to evaluate the influence of an alternating linseed oil (LO) and fish oil (FO) feeding strategy in black seabream A. schlegelii (initial weight, 8.49 ± 0.01 g). Two isonitrogenous and isolipidic feeds were formulated to contain FO or LO, and used to enable three feeding strategy treatments termed FO (feeding the FO diet for 8 weeks), LO (feeding the LO diet for 8 weeks) and FO re-feeding (feeding LO for 4 weeks then FO for 4 weeks). Fish in the FO re-feeding and FO groups had significantly higher final body weights (FBW), weight gains (WG), specific growth rates (SGR) but lower muscle lipid content than fish in the LO group. In muscle, the FO re-feeding strategy restored eicosapentaenoic and docosahexaenoic acid contents to 82.67% and 83.84%, respectively, of those in fish fed the FO treatment. In addition, the FO re-feeding strategy significantly down-regulated the expression levels of genes related to long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis and lipogenesis, including fatty acyl desaturase (fads2), elongase of very long-chain fatty acids 4a (elovl4a) and sterol regulatory element-binding protein-1 (srebp-1) compared to fish fed the LO treatment. Similarly, the hepatic Srebp-1c concentration in fish in the FO re-feeding group was markedly lower than in fish in the LO treatment group. Expression of the lipid catabolism gene adipose triglyceride lipase (atgl) was up-regulated in fish in the FO re-feeding group compared with fish in the LO group. Overall, the present study indicated that a strategy of re-feeding FO following feeding LO for four-week promoted growth, mitigated lipid accumulation in muscle, and effectively restored muscle n-3 LC-PUFA levels in A. schlegelii.

Visible-light photoredox-catalyzed selective carboxylation of C(sp3)−F bonds with CO2

Visible-light photoredox-catalyzed selective carboxylation of C(sp3)−F bonds with CO2

Design, Synthesis and Anticancer Evaluation of Substituted Cinnamic Acid Bearing 2-Quinolone Hybrid Derivatives.

A new series of hybrid molecules containing cinnamic acid and 2-quinolinone derivatives were designed and synthesized. Their structures were confirmed by 1H-NMR, 13C-NMR and mass analyses. All the synthesized hybrid molecules were assessed for their in vitro antiproliferative activity against more than one cancer cell lines. Compound 3-(3,5-dibromo-7,8-dihydroxy-4-methyl-2-oxoquinolin-1(2H)-ylamino)-3-phenylacrylic acid (5a) with IC50 = 1.89 μM against HCT-116 was proved to the most potent compound in this study, as compared to standard drug staurosporin. DNA flow cytometry assay of compound 5a revealed G2/M phase arrest and pre-G1 apoptosis. Annexin V-FITC showed that the percentage of early and late apoptosis was increased. The results of topoisomerase enzyme inhibition activity showed that the hybrid molecule 5a displays potent inhibitory activity compared with control.

Antibacterial constituents from the roots, stem bark and leaves of Manilkara obovata (Sabine & G. Don) J. H. Hemsl. (Sapotaceae)

• Obovacoumaric acid and obovatol were isolated from the methanolic extracts of Manilkara obovata . • A new ethylcanophyllate was obtained by esterification of canophyllic acid. • The structures were elucidated by NMR and single crystal X-ray crystallography. • Antibacterial effects of the methanolic extracts of Manilkara obovata . The investigation of the methanolic extracts of the roots, stem bark and leaves of Manilkara obovata (Sabine & G. Don) J. H. Hemsl. (Sapotaceae), synonym Manilkara argentea Pierre ex Dubard, has led to the isolation and characterization of a new 4-phenylcoumarin derivative, in form of a racemic mixture of obovacoumaric acid ( 1a ) and the previously reported callophyllic acid ( 1b ) as well as a new taraxerane type triterpene named obovatol ( 2 ), alongside twenty-five known compounds. In addition, ethylcanophyllate ( 3a ), obtained by esterification of canophyllic acid ( 3 ) is reported here for the first time. The structures of compounds were determined by comprehensive spectroscopic analyses of their 1D and 2D NMR, EI/ESI-MS and single crystal X-ray diffraction (SC-XRD) analysis for 1a and 1b , accompanied by comparison with reported records. In addition, the antibacterial activity of crude extracts, fractions and some of the isolated compounds including the hemi-synthesized ethylcanophyllate ( 3a ) was determined against Salmonella typhi , Staphylococcus aureus ATCC4330, Enterobacter cloacae , Pseudomonas aeruginosa HM801, Streptococcus pneumoniae ATCC491619 and Escherichia coli ATCC25322 applying the broth microdilution method. While the methanolic stem bark extract showed good to significant activity against all bacterial test strains with MICs between 7.8 and 62.5 μg/mL, its fractions A and B were less active, indicating synergistic effects. This effect was also observed for the methanolic root extract, which gave a significant MIC against Staphylococcus aureus ATCC4330 with MIC < 3.9 μg/mL, but only MICs of 31.2 and 7.8 μg/mL for its fractions D and E. Likewise, though fractions F 3 and F 4 of the methanolic leaf extract displayed good MICs of 31.2 and 15.6 μg/mL, respectively, against Staphylococcus aureus ATCC4330, tested compounds were not stronger active. Interestingly, the hemi-synthesized ethylcanophyllate ( 3a ) based on the completely antibacterial inactive canophyllic acid ( 3 ) displayed a good MIC of 15.6 μg/mL against Staphylococcus aureus ATCC4330, pointing here to a dominant role of the ester function in compound 3a in the structure-activity relationship.

Absolute Configuration Sensing of Chiral Aryl- and Aryloxy-Propionic Acids by Biphenyl Chiroptical Probes

The absolute configuration of chiral 2-aryl and 2-aryloxy propionic acids, which are among the most common chiral environmental pollutants, has been readily and reliably established by either electronic circular dichroism spectroscopy or optical rotation measurements employing suitably designed 4,4′-disubstituted biphenyl probes. In fact, the 4,4′-biphenyl substitution gives rise to a red shift of the diagnostic electronic circular dichroism signal of the biphenyl A band employed for the configuration assignment, removing its overlap with other interfering dichroic bands and allowing its clear sign identification. The largest A band red shift, and thus the most reliable results, are obtained by employing as a probe the 4,4′-dinitro substituted biphenylazepine 3c. The method was applied to the absolute configuration assignment of 2-arylpropionic acids ibuprofen (1a), naproxen (1b), ketoprofen (1c) and flurbiprofen (1d), as well as to the 2-aryloxypropionic acids 2-phenoxypropionic acid (2a) and 2-naphthoxypropionic acid (2b). This approach, allowing us to reveal the sample’s absolute configuration by simple optical rotation measurements, is potentially applicable to online analyses of both the enantiomeric composition and absolute configuration of these chiral pollutants.

Synthesis and anticancer evaluation of some coumarin and azacoumarin derivatives

Abstract Coumarin and its nitrogen analogue 1-aza coumarin are a class of lactones and lactams, respectively, which are indispensable heterocyclic units to both chemists and biochemists. 1-Aza coumarin derivatives, which ultimately metabolize as the corresponding 8-hydroxy coumarins in the biological system are therefore found to be very good anti-inflammatory, anti-cancer, and analgesic agents. A series of hybrid substituted coumarin and azacoumarin-3-carboxylic acid derivatives (8-methoxycoumarin-3-carboxylic acid (4a), 8-methoxyazacoumarin-3-carboxylic acid (4b), 5-bromo-8-methoxycoumarin-3-carboxylic acid (5a), 5-bromo-8-methoxyazacoumarin-3-carboxylic acid (5b), 2-acetoxy-5-bromo-8-methoxyquinoline-3-carboxylic acid (6), and 5,7-di(phenylazo)-8-methoxycoumarin-3-carboxylic acid (7) were synthesized and structurally proved using spectral and elemental analysis data. Substituted coumarin-3-carboxylic acid (4a and 5a) and Substituted azacoumarin-3-carboxylic acid (4b, 5b and 6) were tested for their in vitro cytotoxic activity against MCF-7 and HepG-2 cell lines.

Electrochemical Oxidation Dearomatization of Anisol Derivatives toward Spiropyrrolidines and Spirolactones

Spiro compounds are widely prevalent in biological activities and natural products. However, developing new strategies for their efficient synthesis and derivatization remains a challenge. Outstand...

Conformational evaluation of fusidic acid derivatives by 750 MHz 1H NMR and VCD

Fusidic acid (1a) is a commercial antibiotic widely used in therapy for methicillin-resistant Staphylococcus aureus infections. Although the history of spectroscopic and conformational characteristics of 1a is long and old, the complete 1H NMR parameters set assignment remains incomplete due to the large signal superposition in most conventionally used NMR spectrometers. Thus, in the present study the 750 MHz 1H NMR spectra of the two methyl acetylfusidates 1b and 1c were completely assigned by means of total-line-shape-fitting calculations using the PERCH iterative spectra analysis. The task was facilitated taking advantage of the data for 3β-acetoxypregna-Δ5,16‑dien-20-one and cholesteryl benzoate, thereby allowing to obtain excellent correlations between experimental vicinal coupling constants with values calculated by the Altona program. It turned out that the vicinal coupling constant values were not compatible with the published boat conformation of B-ring. Thus, a vibrational circular dichroism study of 1b and 1c, using density functional theory calculated spectra to compare with experimental spectra, revealed that ring B in these trans-syn-trans 29-nor-protostane triterpenoids exists in equilibrium between two twisted boat conformers. This is very useful for future docking calculations to test the antibiotic in front of proteins to find further specific pharmacological applications.

Rhodanine-3-acetamide derivatives as aldose and aldehyde reductase inhibitors to treat diabetic complications: synthesis, biological evaluation, molecular docking and simulation studies

In diabetes, increased accumulation of sorbitol has been associated with diabetic complications through polyol pathway. Aldose reductase (AR) is one of the key factors involved in reduction of glucose to sorbitol, thereby its inhibition is important for the management of diabetic complications. In the present study, a series of seven 4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetamide derivatives 3(a–g) were synthesized by the reaction of 5-(4-hydroxy-3-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2a) and 5-(4-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2b) with different amines. The synthesized compounds 3(a–g) were investigated for their in vitro aldehyde reductase (ALR1) and aldose reductase (ALR2) enzyme inhibitory potential. Compound 3c, 3d, 3e, and 3f showed ALR1 inhibition at lower micromolar concentration whereas all the compounds were more active than the standard inhibitor valproic acid. Most of the compounds were active against ALR2 but compound 3a and 3f showed higher inhibition than the standard drug sulindac. Overall, the most potent compound against aldose reductase was 3f with an inhibitory concentration of 0.12 ± 0.01 µM. In vitro results showed that vanillin derivatives exhibited better activity against both aldehyde reductase and aldose reductase. The molecular docking studies were carried out to investigate the binding affinities of synthesized derivatives with both ALR1 and ALR2. The binding site analysis of potent compounds revealed similar interactions as were found by cognate ligands within the active sites of enzymes.

SAR insights into TET2 catalytic domain inhibition: Synthesis of 2-Hydroxy-4-Methylene-pentanedicarboxylates

The TET (Ten-Eleven Translocation) dioxygenase enzyme family comprising 3 members, TET1-3, play key roles in DNA demethylation. These processes regulate transcription programs that determine cell lineage, survival, proliferation, and differentiation. The impetus for our investigations described here is derived from the need to develop illuminating small molecule probes for TET enzymes with cellular activity and specificity. The studies were done so in the context of the importance of TET2 in the hematopoietic system and the preponderance of loss of function somatic TET2 mutations in myeloid diseases. We have identified that 2-hydroxy-4-methylene-pentanedicarboxylic acid 2a reversibly competes with the co-substrate α-KG in the TET2 catalytic domain and inhibits the dioxygenase activity with an IC50 = 11.0 ± 0.9 μM at 10 μM α-KG in a cell free system and binds in the TET2 catalytic domain with Kd = 0.3 ± 0.12 μM.

Understanding the molecular mechanism of γ-elimination of nitrous acid in the framework of the molecular electron density theory.

The reactions of γ-dehydronitration of furaxanenitrolic acids have been studied within the density functional theory using molecular electron density theory scheme at the MPWB1K(PCM)/6-311G(d,p) level of theory. The alteration of bonding along the course of the reaction is studied in the topology of the electron density functional within the bonding evolution theory perspective. The characteristics of electron density changes indicate that we can distinguish six different phases in the nitrous acid extrusion from furaxanenitrolic acid 1a. These different phases related to the intrinsic reaction coordinate path of the analyzed reaction denote the non-concerted nature of the molecular mechanism.

A green and efficient synthesis of novel caffeic acid derivatives with Meldrum’s acid moieties as potential antibacterial agents

Electrochemical oxidation of caffeic acid (1) has been studied in the presence of methyl and phenyl Meldrum's acids (3a–3b) as nucleophiles in water/acetonitrile (90/10) solutions using cyclic voltammetry and controlled-potential coulometry methods. The cyclic voltammetric results indicate that a one‐pot two‐step sequential reaction occurs between Meldrum's acids and the electrochemically derived o‐benzoquinone from the oxidation of caffeic acid and new caffeic acid derivatives with Meldrum's acid moieties (5a–5b) is formed. The mechanism of this reaction was suggested as an EC pathway using cyclic voltammetry, controlled-potential coulometry and spectroscopic data. In this work, we introduced the synthesis of new compounds with good yields and enhanced antibacterial activity through a catalyst‐free, environmentally friendly method at room temperature under green conditions. Furthermore, the antibacterial evaluation of caffeic acid (1), methyl and phenyl Meldrum's acids compounds (3a–3b) (as primary substances) in comparison with synthesized compounds (5a–5b) was performed by broth micro-dilution (or micro-dilution) method. Compounds (5a–5b) were found to be more effective against Gram ( −) and Gram ( +) bacteria than primary substances (1, 3a–3b).

Identification of α-glucosidase inhibitors from Cortex Lycii based on a bioactivity-labeling high-resolution mass spectrometry–metabolomics investigation

Cortex Lycii, as a kind of traditional Chinese medicines, have shown prospects in the prevention of diabetes and its complications. However, there is comparatively little information regarding the characterization of potentially hypoglycemic compounds derived from Cortex Lycii. In this study, we performed a global non-selective investigation of α-glucosidase inhibitors in Cortex Lycii based on a bioactivity-labeling high-resolution mass spectrometry–metabolomics method. Samples of Cortex Lycii were collected from different Chinese provinces and their ethyl acetate extracts were analyzed using an in vitro α-glucosidase inhibition assay for bioactivity-labeling. The ethyl acetate extracts were also subjected to liquid chromatography-mass spectrometry analysis and multivariate data analysis was subsequently conducted to identify correlations between the bioactivity measured from the enzyme-involved test and the profiles obtained based on high-resolution mass spectrometry. The variables contributing significantly to the separation of the more-active from the less-active samples were considered to indicate the potential target ions of active compounds. MS/MS fragment patterns and nuclear magnetic resonance analyses were used to identify the potential target ions. The developed platform mentioned above facilitated rapid identification of four α-glucosidase inhibitors, namely, N-p-trans-coumaroyltyramine (1), N-trans-caffeoyl-tyramine (2), (9R,10E,12Z)-9-hydroxy-10,12-octadecadienoic acid (3a), and (9S,10E,12Z)-9-hydroxy-10,12-octadecadienoic acid (3b) from Cortex Lycii. The α-glucosidase inhibitory activities of compounds 3a and 3b with IC50 values of 1.0413±0.0551 and 1.0423±0.0049 mM, respectively, are reported here for the first time. Enzyme kinetics revealed that both 3a and 3b were non-competitive inhibitors of α-glucosidase, with Ki values of 2.20 and 2.24 mM, respectively. In short, the presented work identified compounds 3a and 3b as potential α-glucosidase inhibitors with higher inhibitory activity and a different mode of inhibition compared to the standard α-glucosidase inhibitor, acarbose. The integrated approach adopted in this study can be extended as a normalized procedure to rapidly identify active compounds, even from complex extracts, and can readily be adapted for the study of other natural products.

Metabolite profile of Nectandra oppositifolia Nees & Mart. and assessment of antitrypanosomal activity of bioactive compounds through efficiency analyses.

EtOH extracts from the leaves and twigs of Nectandra oppositifolia Nees & Mart. shown activity against amastigote forms of Trypanosoma cruzi. These extracts were subjected to successive liquid-liquid partitioning to afford bioactive CH2Cl2 fractions. UHPLC-TOF-HRMS/MS and molecular networking were used to obtain an overview of the phytochemical composition of these active fractions. Aiming to isolate the active compounds, both CH2Cl2 fractions were subjected to fractionation using medium pressure chromatography combined with semi-preparative HPLC-UV. Using this approach, twelve compounds (1-12) were isolated and identified by NMR and HRMS analysis. Several isolated compounds displayed activity against the amastigote forms of T. cruzi, especially ethyl protocatechuate (7) with EC50 value of 18.1 μM, similar to positive control benznidazole (18.7 μM). Considering the potential of compound 7, protocatechuic acid and its respective methyl (7a), n-propyl (7b), n-butyl (7c), n-pentyl (7d), and n-hexyl (7e) esters were tested. Regarding antitrypanosomal activity, protocatechuic acid and compound 7a were inactive, while 7b-7e exhibited EC50 values from 20.4 to 11.7 μM, without cytotoxicity to mammalian cells. These results suggest that lipophilicity and molecular complexity play an important role in the activity while efficiency analysis indicates that the natural compound 7 is a promising prototype for further modifications to obtain compounds effective against the intracellular forms of T. cruzi.

Biological Profiling of Semisynthetic C19-Functionalized Ferruginol and Sugiol Analogues

The abietane-type diterpenoids are significant bioactive compounds exhibiting a varied range of pharmacological properties. In this study, the first synthesis and biological investigation of the new abietane-diterpenoid (+)-4-epi-liquiditerpenoid acid (8a) together with several of its analogs are reported. The compounds were generated from the readily available methyl callitrisate (7), which was obtained from callitrisic acid present in Moroccan Sandarac resin. A biological evaluation was conducted to determine the effects of the different functional groups present in these molecules, providing basic structure–activity relationship (SAR) elements. In particular, the ferruginol and sugiol analogs compounds 10–16 were characterized by the presence of a phenol moiety, higher oxidization states at C-7 (ketone), and the hydroxyl, methyl ester or free carboxylic acid at C19. The biological profiling of these compounds was investigated against a panel of six human solid tumor cell lines (HBL-100, A549, HeLa, T-47D, SW1573 and WiDr), four parasitic Leishmania species (L. donovani, L. infantum, L. guyanensis and L. amazonensis) and two malaria strains (3D7 and K1). Furthermore, the capacity of the compounds to modulate gamma-aminobutyric acid type A (GABAA) receptors (α1β2γ2s) is also described. A comparison of the biological results with those previously reported of the corresponding C18-functionalized analogs was conducted.

Synthesis, in vitro cytotoxic and apoptotic effects, and molecular docking study of novel adamantane derivatives.

[4-(Adamantane-1-carboxamido)-3-oxo-1-thia-4-azaspiro[4.4]nonan-2-yl]acetic acid (4a) and [4-(adamantane-1-carboxamido)-8-nonsubstituted/substituted-3-oxo-1-thia-4-azas-piro[4.5]decane-2-yl]acetic acid (4b-g) derivatives were synthesized; their structures were verified by elemental analysis, infrared spectroscopy, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and massspectroscopy data; and their in vitro cytotoxicity activities were investigated against human hepatocellular carcinoma, human prostate adenocarcinoma, and human lung carcinoma cell lines (HepG2, PC-3, and A549, respectively), and a mouse fibroblast cell line (NIH/3T3). All compounds, exceptcompound 4e, were found as cytotoxic, especially on A549 cells as compared with the other cells (selectivity index = 2.01-11.6). As a further step, the effects of compounds 4a-c on apoptosis induction were tested and the expression of selected apoptosis genes was analyzed. Among the selected compounds, compound 4a induced apoptosis remarkably. Moreover, computational calculations of the binding of compounds 4a-c to the BIR3 domain of the human inhibitor of apoptosis protein revealed ligand-protein interactions at the atomistic level and emphasized the importance of a hydrophobic moiety on the ligands for better binding.

Triterpenoids and Semisynthetic Derivatives with Antimicrobial Activities from the Leaves of &amp;lt;i&amp;gt;Caloncoba glauca&amp;lt;/i&amp;gt; (Flacourtiaceae)

Chemical investigation of the MeOH extract from the leaves of C. glauca yielded nine known triterpenoids (1-9) belonging to the cycloartane and friedelane series. Two of these compounds namely glaucartanoic acid A (1) and 3β,21β-dihydroxy-30-nor-(D:A)-friedoolean-20(29)-en-27-oic acid (5) were subjected to chemical derivatizations and afforded five new derivatives: diacetylglaucartanoic acid A (1a), 24-acetylglaucartanoic acid A (1b), glaucartanoic acid A methyl ester (1c), 24-methoxyglaucartanoic acid A methyl ester (1d), and 3β,21β-diacetoxy-30-nor-(D:A)-friedoolean-20(29)-en-27-oic acid (5a). Their structures were assigned based on their NMR and MS data and by comparison with literature values. The MeOH extract, isolated compounds and some new semi-synthetic derivatives were subjected to in vitro antimicrobial assays against a panel of pathogenic microorganisms, including Gram-positive and Gram-negative bacteria, and fungi using broth microdilution method. The MeOH extract displayed activity towards all the tested pathogenic bacterial and fungal strains with good activity (MIC against Staphylococcus aureus ATCC25923 and Shigella flexneri SDINT. Compounds 3 and 5 showed the most potent antimicrobial effect.

Isolation and Characterization of Chemical Constituents from the Crude mExtracts of Crossopteryx Febrifuga (Afzel ex g. don) benth (Rubiaceae) and Evaluation of Their Phytotoxicity and Antioxidant Activity

The aim of this work is to isolate, characterize, and evaluate the antioxidant activity as well as the phytotoxicity of crude extracts and compounds obtained from C. febrifuga. Nine compounds were isolated from leaves, stem bark and roots (methylene chloride/methanol:1/1) crude extracts after repeated silica gel column chromatography corresponding to shanzhiside methyl ester (1), D-mannitol (2), a mixture of two isomeric pentacyclic triterpenes: oleanolic acid (3a) and ursolic acid (3b), 11-methylixoside (4), 3β-urs-12, 20(30)-diene-27,28-dioic acid (5), quinovin glycoside C (6), 3-O-β-D-3-oxo-glucopyranosyl-ursa-12,20(30)-diene-27,28-dioic acid (7) and 3β-(-α-Lrhamnopyranosyloxy)-ursa-12,20(30)-diene-27,28-dioic acid (8). The compound chemical structures were established by studying their 1H and 13C NMR (1D and 2D) and Mass Spectrometry (MS) spectra. The antioxidant capacity of extracts were evaluated using a recently developed electrochemical method consisting in interacting with the superoxide anion radical (O2.-) generated in situ by reduction of air molecular oxygen (O2) in aprotic medium (anhydrous DMF). The antioxidant index is expressed as the amount of extract needed to consume 30% (AI30) of electrogenerated O2.-. The lower is the antioxidant index, the more active the substrate is against O2.-. The stem bark crude extract is the most active with an AI30 of 79.50mg/L while the leaves and root crude extracts showed a moderate activity against O2.- with AI30 of 303.70mg/L and 450.00mg/L respectively. The phytotoxicity study were carried out using a germination test on Lepidium sativum seeds in absence (0mg/L) and in presence of increasing concentrations (10, 100, 500, 1000mg/L) of crude extracts and the isolated compound (1). The following physiological parameters of the seedlings were evaluated 72 hours after the experimentation: germination percentage (G %), germination index (GI), vigor index (VI), relative root growth (RRG %). Root extracts are the most phytotoxic on seed germination with G% ranging from 66.66 to 100% and RRG% from 8.20 to 88.45% while the isolated compound (1) stimulated growth between 10-500mg/L but showed a moderate phytotoxic effect on seedlings above 500mg/L.