Targeted Isolation of Antiviral Labdane Diterpenes from the Bark of Neo-uvaria foetida (Annonaceae) using LC-MS/MS-Based Molecular Networking.

In the search of new inhibitors for human coronavirus (HCoV), we screened extracts of endemic Annonaceae plants on an assay using a cellular model of Huh-7 cells infected with the human alphacoronavirus HCoV-229E. The EtOAc bark extract of the rare Southeast Asian plant Neo-uvaria foetida exhibited inhibition of HCoV-229E and SARS-CoV-2 viruses with IC50 values of 3.8 and 7.8 µg/mL, respectively. Using LC-MS/MS and molecular networking analysis guided isolation, we discovered two new labdane-type diterpenoids, 8-epi-acuminolide (1) and foetidalabdane A (4), and three known labdane diterpenoids, acuminolide (2), 17-O-acetylacuminolide (3), and spiroacuminolide (5). A new norlabdane diterpene, 16-foetinorlabdoic acid (6), was also isolated and identified. Excluding compounds 5 and 6, all other metabolites were active against the virus HCoV-229E. Terpenoids 1 and 4 presented antiviral activity against SARS-CoV-2 with IC50 values of 63.3 and 93.5 µM, respectively, indicating lower potency. Additionally, virological assays demonstrated that compounds 1, 2, and 3 exert antiviral effects against Zika virus by specifically interfering with the late stage of its infectious cycle with IC50 values of 76.0, 31.9, and 14.9 µM, respectively.

Oil palm frond-derived cellulose nanocrystals: Effect of pretreatment and elucidating its reinforcing potential in hydrogel beads.

Herein, cellulose nanocrystals were synthesized from oil palm fronds (CNC-OPF) involving two pretreatment approaches, viz. autohydrolysis and soda pulping. The pretreatments were applied individually to OPF fibers to assess their influence on CNCs' physicochemical and thermal properties. CNC-OPF samples were assessed using complementary characterization techniques, which confirmed their purity and characteristics. CP/MAS 13C NMR and TEM studies revealed that autohydrolysis pretreatment yielded CNCs with effective hemicellulose and extractives removal compared to that of soda pulping. XRD analysis demonstrated that autohydrolysis-treated CNC-OPF contained a much higher crystallinity index compared to soda pulping treatment. BET measurement disclosed a relatively higher surface area and wider pore diameter of autohydrolysis-treated CNC-OPF. Autohydrolysis-treated CNCs were applied as a reinforcement filler in alginate-based hydrogel beads for the removal of 4-chlorophenol from water, which attained a qmax of 19.168 mg g-1. BET analysis revealed the less porous nature of CNC-ALG hydrogel beads which could have contributed to hydrogel beads' relatively lower adsorption capacity. The point of zero charge of CNC-ALG hydrogel beads was 4.82, suggesting their applicability only within a short solution pH range. This study directs future studies to unveil the possibilities of functionalizing CNCs in order to enhance the adsorption performance of CNC-immobilized hydrogel beads towards 4-chlorophenol and other organic contaminants.

Preparation and characterizations of oil palm fronds cellulose nanocrystal (OPF-CNC) as reinforcing filler in epoxy-Zn rich coating for mild steel corrosion protection.

Oil palm frond (OPF) is one of largest contributions to the biomass waste from oil palm plantation. In this work, OPF has been successfully utilized to prepare cellulose nanocrystal (OPF-CNC) by acid hydrolysis. OPF was initially treated with autohydrolysis treatment. The obtained OPF-CNC was characterized via complementary analyses. The produced OPF-CNC showed a high crystallinity index value (60%) and high BET surface area (26.10 m2 g-1) as compared to α-cellulose (crystallinity index: 54% and BET surface area:7.14 m2g-1). The surface analyses via scanning electron microscope (SEM) and transmission electron microscopy (TEM) demonstrated that the OPF-CNC has a smooth surface with a needle-like shape, where the average length and diameter are 95.09 nm and 6.81 nm, respectively. The corrosion analyses via electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization (PD) illustrate that the coated mild steel with the inclusion of 0.5 wt% OPF-CNC has managed to sharply reduce the corrosion (99%). The coated mild steel with the inclusion of 0.5 wt% OPF-CNC showed the highest hydrophobicity (100.5 ± 0.7°) and has lowest amount of O via water contact angle and energy dispersive X-ray spectroscopy (EDX) analyses respectively, indicating lowest corrosion rate.

Corrosion inhibition on mild steel in 1 M HCl solution by Cryptocarya nigra extracts and three of its constituents (alkaloids).

Corrosion inhibition effect of the crude extracts (hexane, dichloromethane, methanol) from the bark of Cryptocarya nigra and three alkaloids named N-methylisococlaurine 1, N-methyllaurotetanine 2 and atherosperminine 3 isolated from the Cryptocarya nigra dichloromethane extract (CNDE) were investigated for mild steel corrosion in 1 M HCl solution. An electrochemical impedance study showed that CNDE and 2 reduced the corrosion significantly through a charge transfer mechanism with inhibition efficiency of 91.05% and 88.05%, respectively. Potentiodynamic polarization data indicated that CNDE acted through anodic type inhibition while 2 was a mixed type inhibitor with predominant anodic effectiveness. ΔG ads values calculated from the Langmuir adsorption isotherm plots for CNDE (-28.2 kJ mol-1) and 2 (-13.2 kJ mol-1) suggested that they adsorbed on the mild steel surface via a physisorption mechanism. Scanning electron microscopy micrographs and elemental composition studies confirmed the formation of a protective film over the metal surface. Wastewater quality parameters of all the inhibitors demonstrated good biodegradability as their values were within the permissible limits to discharge for irrigation and horticultural uses.

In vitro antiplasmodial and antioxidant activities of bisbenzylisoquinoline alkaloids from Alseodaphne corneri Kosterm.

OBJECTIVE: To study antiplasmodial and antioxidant activities of the isolation of alkaloids from the active dichloromethane extract of Alseodaphne corneri. METHODS: Phytochemical studies of the crude extract led to the isolation of six alkaloids using recycle high performance liquid chromatography and preparative thin layer chromatography. The antiplasmodial activity of the isolated compounds was evaluated using the histidine-rich protein II assay. The isolated alkaloids were also tested for their antioxidant activity using three different assays; DPPH, ferric reducing ability of plasma and metal chelating assays. RESULTS: Malaria infection caused the formation of free radicals which subsequently led to oxidative stress and apoptosis. The antioxidant properties of the alkaloids under investigation revealed that in addition to the antiplasmodial activity, the alkaloids could also prevent oxidative stress. (+)-laurotetanine and (+)-norstephasubine exhibited strong antiplasmodial activities with IC50 values of 0.189 and 0.116 µM, respectively. CONCLUSIONS: Interestingly, the two most potent compounds that exhibit antiplasmodial activity also exhibit good antioxidant activities. The crude dichloromethane extract and the isolated compounds exert substantial antiplasmodial and antioxidative activities which in turn suppress oxidative stress and cause less damage to the host.

Ultraviolet-visible study on acid-base equilibria of aporphine alkaloids with antiplasmodial and antioxidant activities from Alseodaphne corneri and Dehaasia longipedicellata.

The UV-vis spectra of isocorydine 1, norisocorydine 2 and boldine 3 were studied in 2% v/v acetonitrile, at constant ionic strength (0.1 M NaCl, 35 degree Celsius). The pK(a) values of isocorydine 1 and norisocorydine 2 were 11.75 and 12.07, respectively. Boldine 3 gave a pK(a) value of 9.16 and 10.44. All of the alkaloids 1-3 were stable at physiological pH; thereby all of them will not ionize, thus permitting the basic nitrogen to be protonated and accumulated within the acidic food vacuole of Plasmodium via pH trapping. Subsequently, acidic food vacuoles that have been neutralized by alkaloids would result in enhancement of the antiplasmodial activity. The alkaloids showed antiplasmodial activity against Plasmodium falciparum and antioxidant activities; DPPH radical scavenging, metal chelating and ferric reducing power. The antioxidant properties of the alkaloids under investigation revealed that in addition to the antiplasmodial activity, the alkaloids can also prevent oxidative damage. It can be prevented by binding free heme and neutralizing the electrons produced during the Plasmodium falciparum mediated haemoglobin destruction in the host. Slightly basic properties of the aforementioned alkaloids, along with their antioxidant activities, are advantageous in improving the suppression of malaria infection that cause less damage to the host.

Antiplasmodial and antioxidant isoquinoline alkaloids from Dehaasia longipedicellata.

The crude extract of the bark of Dehaasia longipedicellata exhibited antiplasmodial activity against the growth of Plasmodium falciparum K1 isolate (resistant strain). Phytochemical studies of the extract led to the isolation of six alkaloids: two morphinandienones, (+)-sebiferine (1) and (-)-milonine (2); two aporphines, (-)-boldine (3) and (-)-norboldine (4); one benzlyisoquinoline, (-)-reticuline (5); and one bisbenzylisoquinoline, (-)-O-O-dimethylgrisabine (6). Their structures were determined on the basis of 1D and 2D NMR, IR, UV, and LCMS spectroscopic techniques and upon comparison with literature values. Antiplasmodial activity was determined for all of the isolated compounds. They showed potent to moderate activity with IC50 values ranging from 0.031 to 30.40 µM. (-)-O-O-dimethylgrisabine (6) and (-)-milonine (2) were the two most potent compounds, with IC50 values of 0.031 and 0.097 µM, respectively, that were comparable to the standard, chloroquine (0.090 µM). The compounds were also assessed for their antioxidant activities with di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (IC50 = 18.40-107.31 µg/mL), reducing power (27.40-87.40 %), and metal chelating (IC50 = 64.30 to 257.22 µg/mL) having good to low activity. (-)-O-O-dimethylgrisabine (6) exhibited a potent antioxidant activity of 44.3 % reducing power, while di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium and metal chelating activities had IC50 values of 18.38 and 64.30 µg/mL, respectively. Thus it may be considered as a good reductant with the ability to chelate metal and prevent pro-oxidant activity. In addition to the antiplasmodial and antioxidant activities, the isolated compounds were also tested for their cytotoxicity against a few cancer and normal cell lines. (-)-Norboldine (4) exhibited potent cytotoxicity towards pancreatic cancer cell line BxPC-3 with an IC50 value of 27.060 ± 1.037 µM, and all alkaloids showed no toxicity towards the normal pancreatic cell line (hTERT-HPNE).

Antiplasmodial alkaloids from the bark of Cryptocarya nigra (Lauraceae).

A dichloromethane extract of the stem bark of Cryptocarya nigra showed strong in vitro inhibition of Plasmodium falciparum growth, with an IC50 value of 2.82 µg/mL. The phytochemical study of this extract has led to the isolation and characterization of four known alkaloids: (+)-N-methylisococlaurine (1), atherosperminine (2), 2-hydroxyathersperminine (3), and noratherosperminine (4). Structural elucidation of all alkaloids was accomplished by means of high field 1D- and 2D-NMR, IR, UV and LCMS spectral data. The isolated extract constituents (+)-N-methylisococlaurine (1), atherosperminine (2) and 2-hydroxy-atherosperminine (3) showed strong antiplasmodial activity, with IC50 values of 5.40, 5.80 and 0.75 µM, respectively. In addition, (+)-N-methylisocolaurine (1) and atherosperminine (2) showed high antioxidant activity in a DPPH assay with IC50 values of 29.56 ug/mL and 54.53 ug/mL respectively. Compounds 1 and 2 also both showed high antioxidant activity in the FRAP assay, with percentages of 78.54 and 70.66 respectively and in the metal chelating assay, with IC50 values of 50.08 ug/mL and 42.87 ug/mL, respectively.

Lancifoliaine, a new bisbenzylisoquinoline from the bark of Litsea lancifolia.

A new bisbenzylisoquinoline, lancifoliaine (1), together with seven known alkaloids--N-allyllaurolitsine (2), reticuline (3), actinodaphnine, norboldine, pallidine, cassythicine and boldine--were isolated from the stem bark of Litsea lancifolia (Lauraceae). In addition to that of lancifoliaine, complete ¹³C-NMR data of N-allyl-laurolitsine (2) was also reported. The alkaloidal structures were elucidated by means of high field 1D- and 2D-NMR IR, UV, and LCMS-IT-TOF spectral data. N-Allyllaurolitsine (2) showed a moderate vasorelaxant activity on isolated rat aorta.