Search

AbstractCurrent sickle cell disease (SCD) therapies are limited and inefficient. The ethnomedicinal values of Annona muricatain the treatment of SCD, leading to this present research. Leaves and fruits of Annona muricatawere processed using solvent extraction and partitioning; aqueous, chloroform and ethyl acetate fractions. In vitro(anti-oxidant and anti-sickling), in silico, quantitative (amino acids) and kinetic simulation experiments were done. 15-acetyl guanacone, was used, in silicoagainst 2,3-bisphosphoglycerate (2, 3-BPG) mutase and deoxyhaemoglobin. The ethyl acetate and chloroform fractions better NO●scavengers, iron-chelators and ferric reducing. In vitrounsickling (UT50) had ethyl acetate = 5 h and methanol = 7 h. Chloroform fraction had EC501.00 mg/mL (EC50= 546 mg/mL) to 10.00 mg/mL (EC50= 99 mg/mL). EC50and IC50of ethyl acetate fraction had steady-decrease. At higher concentration, chloroform fraction had higher Bmax(1.48 × 1021U/mL) and higher Kd(3.66 × 1019 mg/mL), whereas, at a lower concentration, the ethyl acetate fraction demonstrated higher Bmax(7.23 × 1012U/mL) and lower Kd(2.12 × 1011 mg/mL); The relative affinity (BP) of chloroform fraction increased progressively with concentration. The amino acid profile revealed rich concentrations glycine, valine, leucine, lysine, phenylalanine, histidine, arginine, and tryptophan. From the in silicoexperiments, 15-acetyl guanacone specifically targeted the A and B chains, with greater affinity for the beta subunit. This suggested that 15-acetyl guanacone might be able to prevent the polymerisation of deoxyHbSS, induce an allosteric conformational change that increases the oxygen affinity, and decrease the cellular 2, 3-BPG concentration.Communicated by Ramaswamy H. Sarma

Annona muricatahas been attributed with numerous health benefits – including anticancer properties. The aim of this study was to carry out anticancer investigations of fractions of Annona muricata, by isolating a key compound and assessing antioxidant properties. The anticancer properties of fractions of Annona muricatawere assessed using cell lines, and the potent fractions were subjected to isolation procedures. The isolated compound was examined using standard spectroscopies and further assayed with fractions for antioxidant properties. The cell viability of the most potent fractions revealed that ethyl acetate fruit (EAF, 10.62%) and ethyl acetate leaf (EAL, 10.83%) had the highest anticancer abilities, followed by ethyl acetate root-bark (11.44%), crude methanol leaf extract (16.21%) and crude methanol fruit extract (53.50%). The bi-phasic effect was observed for ethyl acetate fruit. The “reverse cycle S-G2 phase disproportionation” pattern was also observed with EAF and EAL. EAF caused a significant reduction of integrins leading to a decline in cell – cell interactions and increased cell death. The isolated compound demonstrated the presence of α, β-unsaturated γ-lactone and hydroxyl functional groups and molecular weight, 662.4 arriving at a molecular formula of C39H66O8and elucidated as 15-acetyl guanacone. The observations from antioxidant assays suggested that 15-acetyl guanacone possessed a better antioxidant potential compared to fractions. The superior antioxidant properties of EAF compared to EAL correlated significantly with 15-acetyl guanacone (r = 0.563 and r = 0.682, respectively). Thus, the possible in vitroanticancer mechanisms of Annona muricatacould be attributed to pro-apoptotic, bi-phasic and karyokinesis effects, “reverse-cycle S-G2 phase disproportionation”, and inhibition of integrin and antioxidant capacity.

A phytochemical investigation on the chloroform extract of Caesalpinia pulcherrima roots led to the isolation often known furanocassane diterpenoids, vouacapen-5α-ol (1), 8,9,11,14-didehydrovouacapen-5α-ol (2), 6β-cinnamoyl-7β-hydroxyvouacapen-5α-ol (3), pulcherrin A (4), pulcherrin B (5), pulcherrin J (6), pulcherrimin A (7), pulcherrimin B (8), pulcherrimin C (9), and pulcherrimin E (10). Chemical transformation of 3 and 7 gave compounds 6β-hydroxyisovouacapenol C(11), 6β-cinnamoyl-7β-acetoxyvouacapen-5α-ol (12), and pulcherrimin D (13). Cytotoxicity of compounds 1-13 was evaluated against three cancer cell lines (MCF-7, HeLa, and PC-3). Anti-inflammatory potential of the compounds was evaluated via the oxidative burst assay using a luminol-amplified chemiluminescence technique. Leishmanicidal activity was tested against promastigotes of Leishmania major in vitro. Compounds 3,4,8, 9, and 10 were found active against all three cancer cell lines with IC50s ranging from 7.02 ± 0.31 to 36.49 ± 1.39 µM. Compounds 8 and 13 exhibited a potent inhibitory effect on reactive oxygen species generated from human whole blood phagocytes (IC50 = 15.30 ± 1.10 µM and 8.00 ± 0.80 µM, respectively). Compounds 3, 9, and 13 showed significant activity against promastigotes of L. major (IC50 = 65.30 ± 3.20, 58.70 ± 2.80, and 55.90 ± 2.40 µM, respectively). [ABSTRACT FROM AUTHOR]

The TiCl4-mediated cyclization of 1,3-bis(silyloxy)-1,3-butadienes with 2-acetyl-1-silyloxybut-1- en-3-one and 3-acetyl-4-silyloxypent-3-en-2-one, readily available from 3-(formyl)acetylacetone and 3-(acetyl)acetylacetone (triacetylmethane), afforded a variety of functionalized acetophenones

Chromatographic fractionation of the methanolic extract of Asteriscus hierochunticus whole plant led to the identification of a new humulene glucoside (1). The chemical structure of the isolated compound was elucidated by IR, 1D, 2D NMR, and HRESIMS data analysis to be (-)-(2Z,6E,9E)8α-hydroxy-2,6,9-humulatrien-1(12)-olide. In this study, we report the in silico binding affinities of 1 against four different SARS-CoV-2 proteins (COVID-19 main protease (PDB ID: 6lu7), nonstructural protein (PDB ID: 6W4H), RNA-dependent RNA polymerase (PDB ID: 7BV2), and SARS-CoV-2 helicase (PDB ID: 5RMM)). The isolated compound showed excellent binding affinity values (ΔG) of −21.65, −20.05, −28.93, and −21.73 kcal/mol, respectively, against the target proteins compared to the cocrystallized ligands that exhibited ΔG values of −23.75, −17.65, −23.57, and −15.30 kcal/mol, respectively. Further in silico investigations of the isolated compound (1) for its ADMET and toxicity profiles revealed excellent drug likeliness. On the other hand, the results obtained from in vitro antitrypanosomal, antileishmanial, and antimalarial activities of (1) were not promising.

Jatropha gossypifoliaroot bark is used in ethnomedicine for bacterial infections and cancer of the lungs. Phytochemical investigation resulted in the isolation and characterization of a potent anticancer and novel lathyrane diterpenoid compound, abiodone, with an unusual methylene group. The structure of this novel compound was established by 1D, and 2D NMR spectroscopic experiments and confirmed by X-ray analysis.