Inhibitory activity of limonoids from Khaya grandifoliola C.DC (Meliaceae) against hepatitis C virus infection in vitro

Objective: A fraction from Khaya grandifoliola has recently been shown to inhibit hepatitis C virus (HCV) infection and three limonoids (17-epi-methyl-6-hydroxylangolensate, 7-deacetoxy-7-oxogedunin and 7-deacetoxy-7R-hydroxygedunin) were purified from this fraction. The present study aimed at assessing the inhibitory effect of these limonoids on HCV using cell-culture derived HCV (HCVcc) system. Materials and Methods: Cytotoxic effects of the limonoids on Huh7.5 cells were assessed by MTT assay. Huh7.5 cells were transfected with RNA transcripts of the plasmid Jc1/GLuc2a, carrying a Gaussia luciferase reporter gene to rescue the HCVcc particles which were used to infect naïve cells in the presence or absence of the studied limonoids during 72 hr. Infection and replication rates were monitored by luciferase reporter assay and immunofluorescence assay (IFA) while cellular gene expression was analyzed by western blot, respectively. Results: The limonoids inhibited HCV infection mostly by targeting entry and replication stage. Their inhibitory effect on entry step, comparable to that of anti-CD81 antibody, was related to the blocking of CD81 receptor. In the replication step, the limonoids decreased the expression of NS5B similar to danoprevir. These compounds also significantly decreased but up-regulated the expression of Class-III phosphatidylinositol 4-kinase alpha and 2’,5’-oligoadenylate synthase-3, respectively. Conclusion: The present findings suggest that limonoids from K. grandifoliola are potential anti-HCV agents and may offer an advantage in the treatment of HCV infection

Natural compounds isolated from African mistletoes (loranthaceae) exert anti-inflammatory and acetylcholinesterase inhibitory potentials : in vitro and in silico studies

DATA AVAILABILITY STATEMENT: All data generated or analysed during this study are included in this published article.Please read abstract in article.The Central University of Technology operational expenses and the National Research Foundation (NRF) of South Africa.https://www.mdpi.com/journal/applsciParaclinical Science

In vitro antiproliferative, anti-inflammatory effects and molecular docking studies of natural compounds isolated from Sarcocephalus pobeguinii (Hua ex Pobég)

DATA AVAILABILITY STATEMENT : The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.BACKGROUND : Sarcocephalus pobeguinii (Hua ex Pobég) is used in folk medicine to treat oxidative-stress related diseases, thereby warranting the investigation of its anticancer and anti-inflammatory properties. In our previous study, the leaf extract of S. pobeguinii induced significant cytotoxic effect against several cancerous cells with high selectivity indexes towards non-cancerous cells. AIM : The current study aims to isolate natural compounds from S. pobeguinii, and to evaluate their cytotoxicity, selectivity and anti-inflammatory effects as well as searching for potential target proteins of bioactive compounds. METHODS : Natural compounds were isolated from leaf, fruit and bark extracts of S. pobeguinii and their chemical structures were elucidated using appropriate spectroscopic methods. The antiproliferative effect of isolated compounds was determined on four human cancerous cells (MCF-7, HepG2, Caco-2 and A549 cells) and non-cancerous Vero cells. Additionally, the anti-inflammatory activity of these compounds was determined by evaluating the nitric oxide (NO) production inhibitory potential and the 15-lipoxygenase (15-LOX) inhibitory activity. Furthermore, molecular docking studies were carried out on six putative target proteins found in common signaling pathways of inflammation and cancer. RESULTS : Hederagenin (2), quinovic acid 3-O-[α-D-quinovopyranoside] (6) and quinovic acid 3-O-[β-D-quinovopyranoside] (9) exhibited significant cytotoxic effect against all cancerous cells, and they induced apoptosis in MCF-7 cells by increasing caspase-3/-7 activity. (6) showed the highest efficacy against all cancerous cells with poor selectivity (except for A549 cells) towards noncancerous Vero cells; while (2) showed the highest selectivity warranting its potential safety as a chemotherapeutic agent. Moreover, (6) and (9) significantly inhibited NO production in LPS-stimulated RAW 264.7 cells which could mainly be attributed to their high cytotoxic effect. Besides, the mixture nauclealatifoline G and naucleofficine D (1), hederagenin (2) and chletric acid (3) were active against 15-LOX as compared to quercetin. Docking results showed that JAK2 and COX-2, with the highest binding scores, are the potential molecular targets involved in the antiproliferative and anti-inflammatory effects of bioactive compounds. CONCLUSION : Overall, hederagenin (2), which selectively killed cancer cells with additional anti-inflammatory effect, is the most prominent lead compound which may be further investigated as a drug candidate to tackle cancer progression.The Central University of Technology operational expenses and the National Research Foundation (NRF), South Africa. The APC was funded by the Central University of Technology research expenses (TM).http://www.frontiersin.org/Pharmacologyam2024Paraclinical SciencesSDG-03:Good heatlh and well-bein

Synthesis and anticancer activity evaluation of some new 1,2,3,5-tetrazine derivatives attached to benzothiazole moiety

A series of novel tetrazine derivatives, containing benzothiazole framework, were prepared during the coupling reactions of some diazotized 2-aminobenzo[d]thiazole derivatives with p-acetaminophen. Their structures were elucidated based on NMR and MS spectrometry. The anticancer activity and the safety of the synthesized compounds along with the entire precursors were assessed against three human cancer cell lines and a normal cell line. All the synthesized compounds showed selective cytotoxic activity against the cancer cell lines used in comparison to the normal Vero cell line. Their IC50 values varied from 2.02 to 171.67 μM.The Cameroonian Ministry of Higher Education special research allocation, the German Academic Exchange Service (DAAD) and the University of Pretoria.https://www.arkat-usa.org/arkivoc-journalam2023Paraclinical Science

Cytotoxicity, nitric oxide and acetylcholinesterase inhibitory activity of three limonoids isolated from Trichilia welwitschii (Meliaceae)

BACKGROUND: Limonoids are highly oxygenated compounds with a prototypical structure. Their occurrence in the plant kingdom is mainly confined to plant families of Meliaceae and Rutaceae. Owing to their wide range of pharmacological and therapeutic properties, this study was aimed at investigating the potential nitric oxide (NO) and acetylcholinesterase (AChE) inhibitory activity and the cytotoxicity of three limonoids: trichilia lactone D5 (1), rohituka 3 (2) and dregeanin DM4 (3), isolated from Trichilia welwitschii C.DC RESULTS: Results indicated that the three limonoids had low cytotoxicity towards Vero cells with LC50 values ranging from 89.17 to 75.82 (μg/L. Compounds (2) and (3) had lower cytotoxicity compared to puromycin and doxorubicin used as reference cytotoxic compounds. Compound (1) (LC50 of 23.55 (μg/L) had good antiproliferative activity against RAW 264.7 cancer cells. At the lowest concentration tested (0.5 μg/mL), compound (2) and (3) released the lowest amount of nitric oxide (2.97 and 2.93 μM, respectively). The three limonoids had anti-AChE activity with IC50 values ranged of 19.13 (μg/L for (1), 34.15 (μg/L for (2) and 45.66 (μg/L for (3), compared to galantamine (IC50 of 8.22 ( g/mL) used as positive control CONCLUSION: The limonoid compounds studied in this work inhibited nitric oxide production in LPS-stimulated macrophages and had anti-AChE activity. Trichilia lactone D5 had potential antiproliferative activity against RAW 264.7 cancer cells. The limonoids had low cytotoxicity towards Vero cells lines. This study provided further examples of the importance of limonoids compounds as potential AChE inhibitors and anti-inflammatory agents targeting the inhibition of NO productio

Crystal structure of limonoid TS3, isolated from Trichilia rubescens

The title limonoid compound, C26H28O5·0.5H2O (TS3) [systematic name: (3aS,3bS,4aS,5aS,6S,7aR,8aR,8bS,11aR)-6-(furan-3-yl)-3a,5a,8b,11a-tetramethyl-3a,4a,5,5a,6,7,7a,8b,11,11a-decahydrooxireno[2′,3′:4b,5]oxireno[2′′,3′′:2′,3′]cyclopenta[1′,2′:7,8]phenanthro[10,1-bc]furan-3(3aH)-one hemihydrate], crystallizes with two independent molecules (1 and 2) in the asymmetric unit and one water molecule. TS3 is composed of three six-membered rings (A, C and D), three five-membered rings (B, E and F) and two epoxide rings. A group of five fused rings (A–E) is bonded to a furan ring (F) with a Csp3—Csp2 bond [1.500 (3) Å in molecule 1 and 1.499 (3) Å in molecule 2]. The absolute structures of the molecules in the crystal were determined by resonant scattering; Flack parameter = 0.05 (5). In the crystal, the individual molecules stack in columns along the b-axis direction. The water molecule bridges molecules 1 and 2 via Owater—H...O and C—H...Owater hydrogen bonds. Together with further C—H...O hydrogen bonds, linking molecules 1 and 2, the columns are linked to form slabs parallel to the ab plane. Within each column, molecules are also linked via C—H...π interactions involving the five-membered furan (F) rings

Phytochemical analysis with free radical scavenging, nitric oxide inhibition and antiproliferative activity of Sarcocephalus pobeguinii extracts

Abstract Background Free radicals have been implicated in the pathogenesis of diverse metabolic disorders including cancer. Therefore, fighting against free radicals has become an important strategy in the prevention or treatment of such diseases, in addition to direct or indirect anticancer chemotherapy. Sarcocephalus pobeguinii has been used traditionally to treat various diseases in which excess production of free radicals is implicated, warranting investigation of its free radical scavenging, anticancer and anti-inflammatory activity. Methods In the present study, extracts from leaves, fruits, roots and bark of Sarcocephalus pobeguinii were evaluated on four human cancer cell lines (MCF-7, HeLa, Caco-2 and A549 cells) and a non-cancerous cell line for their antiproliferative potential. The cells were incubated with the plant extracts for 48 h at 37 °C in a 5% CO2 humidified environment and their cytotoxic effect was determined using the tetrazolium-based colorimetric (MTT) assay. The radical inhibition was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging techniques. The nitric oxide inhibitory activity was determined using LPS-activated RAW 264.7 macrophages. The correlation between radical scavenging capacity and antiproliferative activity was also analysed. Results The extract from leaves of Sarcocephalus pobeguinii (LSP) exhibited the highest cytotoxic effect on all four of the human cancer cell lines but with some cytotoxicity to the normal Vero cells. However, the LSP extract had the best selectivity index, ranging from 3.15 to 18.28. Also, antioxidant and anti-inflammatory assays indicated that the LSP extract had the highest radical scavenging capacity of all the extracts. A positive linear correlation was found between free radical scavenging ability and antiproliferative activity against the four cancer cell lines, with the highest correlation factor (R2 = 0.9914) obtained between DPPH inhibition and antiproliferative activity against A549 cells. Conclusions The high selectivity index of the Sarcocephalus pobeguinii leaf extract indicates the potential of using this extract in cancer therapy. Furthermore, the positive correlation between free radical scavenging and antiproliferative activity suggests that the radical scavenging capacity of extracts may contribute to a prediction of their anticancer property

Electronic Structure, Spectroscopic (IR, Raman, UV-Vis, NMR), Optoelectronic, and NLO Properties Investigations of Rubescin E (C31H36O7) Molecule in Gas Phase and Chloroform Solution Using Ab Initio and DFT Methods

Quantum chemical methods were used to study the electronic structure and some physicochemical properties of Rubescin E molecule. Good agreement with experiment was found for J3H-H coupling constant, IR, 1H NMR, and 13C NMR. The excitation energy and oscillator strength calculated by TD-DFT also complement with experiment. Large values were obtained for dipole moment, polarizability, first static hyperpolarizability, electric susceptibility, refractive index, and dielectric constant, meaning that Rubescin E has strong optical and phonon application and can be a good candidate as NLOs material. The 3D analysis of the title molecule leads us to the conclusion that electron can easily be transferred from furan to tetrahydrofuran ring. The global reactivity descriptors were evaluated. Mulliken, ESP, and NBO charges comparisons were carried out and described

Selective cytotoxic activity of isolated compounds from Globimetula dinklagei and Phragmanthera capitata (Loranthaceae)

This study aimed to evaluate the selective cytotoxicity of six natural compounds on four cancerous cells (MCF-7, HeLa, Caco-2 and A549) and two normal intestinal and lung cells (Hs1.Int and Wl-38) cells. We also attempted to analyze basically the structure–activity relationships and to understand the mechanism of action of active compounds using the Caspase-Glo® 3/7 kit. Globimetulin B (2) isolated from Globimetula dinklagei was significantly cytotoxic on cancerous cells with 50% inhibitory concentrations (IC50) ranging from 12.75 to 37.65 μM and the selectivity index (SI) values varying between 1.13 and 3.48 against both normal cells. The compound 3-O-β-d-glucopyranosyl-28-hydroxy-α-amyrin (5) isolated from Phragmanthera capitata exhibited the highest cytotoxic activity on HeLa cells with the IC50 of 6.88 μM and the SI of 5.20 and 8.71 against Hs1.Int and Wl-38 cells, respectively. A hydroxyl group at C-3 of compounds was suggested as playing an important role in the cytotoxic activity. The induction of caspase-3 and -7 activity represents some proof that apoptosis has occurred in treated cells. Globimetulin B (2) selectively killed cancer cells with less toxicity to non-cancerous cells as compared to conventional doxorubicin therapy.https://www.degruyter.com/view/j/znc2021-03-26hj2020Paraclinical Science