C‐28 esterification enhances the cytotoxicity of madecassic acid derivatives against HepG2 and KB cells

The structural modification of madecassic acid focused on the contraction of the six-membered A-ring to a five-membered ring, combined with the dehydration of 6-OH to form a new double bond and formation of the esterification or amidation at C-28. The synthesised structures were identified based on the analysis of their NMR and EIS-MS data. Eighteen new madecassic acid analogues were tested in vitro for their cytotoxicity against three cancer cell lines, including human mouth carcinoma (KB), human hepatocellular carcinoma (HepG2), and human lung carcinoma (A549) using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Among them, compounds 5 and 12 exhibited potent and selective cytotoxic activity in KB and HepG2 cell lines, with IC50 values ranging from 3.57 to 6.32 µM. The results also indicated that analogues with a 5-membered A-ring containing an α,β-unsaturated aldehyde esterified at C-23 showed a decrease in their cytotoxic activity compared to precursors in the tested cancer cells.

Cannabigerol (1, CBG), methyl 4-[(2E)-3,7-dimethyl-2,6-octadienyl)oxy]-3-methoxybenzoate (2, DTM), 5-fluorouracil (3, FU) as a reference, and cannabidiol (4, CBD) were tested for their growth inhibitory effects against KB(ATCC NO, OCL 17) cell lines using two different assays, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazoliumbromide (MTT) assay and the sulforhod-amine B protein (SRB) assay. These compounds showed inhibitory activity in vitro in the micromolar range against KB cell lines. In general, the antitumor activities of these compounds (1, 2, 3 and 4) were dose-dependent over the micromolar concentration range of 1 to 100 M. The comparison of IC50 values of these compounds in tumor cell lines showed that their susceptibility to these compounds decreases in the following order: DTM > CBD > 5-FU > CBG by MTT assay and DTM = CBD > 5-FU > CBG by SRB assay. CBG 1, DTM 2, 5-FU 3, and CBD 4 were tested for their cytotoxic effects on NIH 3T3 fibroblasts using two different assays, the MTT assay and SRB assay. These compounds exhibited potent cytotoxic activities in vitro in the micromolar range against NIH 3T3 fibroblasts. In general, the cytotoxic activities of these compounds (1, 2, 3 and 4) were dose-dependent over the micromolar concentration range of 1 to 100 M. The comparison of CD50 values of these compounds in NIH 3T3 fibroblasts shows that their susceptibility to these compounds in decreases the following order(:) CBD > 5-FU > DTM > CBG by MTT assay, CBD > 5-FU > CBG > DTM by SRB assay. These results suggest that DTM 2 has the most growth-inhibitory activity against KB cell lines.

The plant Aeschynomene fascicularis (Fabaceae) has been used in Mayan traditional medicine in the Yucatan peninsula. However, the compounds present in the plant responsible for its curative properties have not yet been investigated. Aeschynomene fascicularis root bark was extracted with 100% methanol to obtain a crude extract. The methanol extract was partitioned successively with solvents with increasing polarity to obtain the corresponding hexane (Hx), dichloromethane (DCM) and ethyl acetate fractions (EtOAc), as well as a residual water-alcoholic fraction. These fractions were tested for their cytotoxic activities using an MTT assay against Hep-2 cancer cell lines. The Hx fraction led to the isolation of spinochalcone C (1), spinochalcone A (2), isocordoin (3) and secundiflorol G (4). Their structures were identified based on spectroscopic evidence and chemical properties. All compounds were subjected to cytotoxicity and antiproliferative assays against a panel of seven cell lines, including one normal-type cell line. Spinochalcone A (2) exhibited cytotoxic activity against DU-145 cell line and antiproliferative activity against the KB cell line. Secundiflorol G (4) showed strong cytotoxic activity towards KB and Hep-2 cell lines. In addition, isocordoin (3) showed moderate activity on KB, Hep-2 and DU-145 cell lines. The active Compounds 2, 3 and 4 are potential therapeutic entities against cancer.

Twenty-eight compounds, including 24 new (4–22, 25–26, and 28–30) and four known (2, 23, 24, and 27) have been synthesized starting from asiatic acid (1), which was isolated from Centella asiatica. The preparation procedure included the acetylation, hydrolyzation on the 2-, 3-, 23-, and the side chain hydroxyl, amino groups, as well as the amidation of the 28-carboxylic group. All the synthesized derivatives were structurally confirmed by 1H, 13C NMR, and MS spectra. Besides, they were evaluated for their cytotoxicity against three cancer cell lines: KB (human carcinoma in the mouth), HepG2 (human hepatocellular carcinoma), and SK-LU-1 (human lung carcinoma). Eleven of the tested compounds, including nine newly synthesized and two known ones showed very strong activity against three tested cell lines with the IC50 values ranging from 0.67 to 37.39 µM. Three compounds showed good activity against KB and HepG2 cell lines with the IC50 values ranging from 1.95 to 32.12 µM. The activity against the KB and HepG2 cell lines was in general higher than that against the SK-LU-1 cell line. The acetylation of the hydroxyl groups in the A-ring and the OH or NH groups in the amide side chains strongly enhanced the activity of the compounds. In addition, five potent compounds (9, 12, and 15–17) were also evaluated for apoptosis-inducing activities. The ratio of apoptosis and necrotic cells increased when lung cancer cells were treated with these compounds. On the other hand, compound 9 increased caspase 3 activities (P < 0.05). Thus, these compounds induced lung cancer cell death by apoptosis and necrosis.

Anti-proliferative activity of essential oil extracted from Thai medicinal plants on KB and P388 cell lines

Several studies have revealed that certain naturally occurring medicinal plants inhibit the growth of various cancers. The present study was conducted to evaluate cytotoxicity and apoptotic induction potential of Myristica fragrans Houtt mace extract. The cytotoxic activity of the Myristica fragrans Houtt mace acetone extract was assayed by MTT assay on human oral epidermal carcinoma KB cell lines. KB cells were incubated with different concentration of mace extract ranging from 25 to 125 μg/mL for 24hrs. The apoptotic induction potential was also studied by the analysis of Bcl-2 protein and gene expression in mace extract incubated KB cell lines using western blotting technique and real-time polymerase chain reaction. The mace extract exhibited cytotoxicity and anticancer effect against KB cell lines and it also suppressed the growth of cancer cells, therefore growth inhibitory effect was noted in extract treated cell lines. The apoptotic potential of mace extract was accompanied by reduced gene expression of Bcl-2 compared to the untreated KB cells. The mace extract shows the cytotoxic activity and induced the apoptosis through the modulation of its target genes Bcl-2 in the KB cell lines, suggesting the potential of mace as a candidate for oral cancer chemoprevention. This can be further investigated in vivo for its anticancer potential.

Background and Objectives:The perpetual search is on to find botanical complementary adjuncts to the conventional therapies used that is not only cost-effective but also reduces side effects associated with conventional synthetic drugs that are available in the market. The aim of this study was to assess the in vitro anticancer efficacy of hydroalcoholic fruit extract of cranberry against oral cancer KB cell line by Di-Methyl Thiazoldiphenyl Tetrazolium bromide assay (MTT) assay and its cytotoxicity on normal fibroblast cells.Materials and Methods:Vaccinium macrocarpon extract was prepared using a hydroethanolic solvent (water – 30%:ethanol – 70%) using the standardized maceration protocol. Standard KB and normal fibroblast (L929) cell lines were used. The minimum lethal effect of the extract was calculated using the MTT cytotoxicity assay.Results:The extract shows a satisfactory antiproliferative effect on the KB cell line and a higher cell viability percentage of the normal fibroblast cell line.Conclusion:V. macrocarpon can prove to be an adjunct to the existing anticancer drug therapy against oral cancer KB cell line.

In Thai Traditional medicine, the leaf of Thai Noni (Yor, Morinda citrifolia Linn.) is used for the treatment of several symptoms including cough, vomiting and pain [1]. However, scientific evidence of the benefits of the noni leaf is limited. In this study, Thai Noni leaves were extracted by several methods and were evaluated against human cancer cell lines: KB (human epidermoid carcinoma), HeLa (human cervical carcinoma), MCF-7 (human breast carcinoma) and HepG2 (human hepatocellular carcinoma) cell lines as well as vero (African green monkey kidney cell) cell line employing the MTT colorimetric method [2], comparing to damnacanthal, rutin, and scopoletin. The dichloromethane extract of fresh leaf showed better inhibitory effect against KB and HeLa cells with IC50 values of 21.67 and 68.50µg/ml, respectively. In a similar way, the dichloromethane extract of dried leaves revealed cytotoxicity against KB cell with IC50 values of 39.00µg/ml, whereas lyophilized, decoction, ethanolic and methanolic extracts as well as the single compounds; rutin and scopoletin, showed reduced anti-proliferative effect in all cancer cell lines (IC50 103-&gt;600µg/ml). Interestingly, damnacanthal showed potent cytotoxicity against either all cancer cell lines or vero cell lines.

A new flavonoid, macatanarin D (1), together with five known stilbenes (2-6), was isolated from fruit glandular trichomes of Macaranga tanarius. Their structures were elucidated on the basis of spectroscopic methods and through comparison with data reported in the literature. All isolated compounds were evaluated for their cytotoxic activities against KB and MCF-7 cell lines. Compounds 3, 4, and 5 showed the strongest activities against both cell lines with IC50 values in the range of 0.03–0.12 μM, and compound 2 only showed a significant cytotoxicity against KB cell line (IC50 = 0.26 μM) and a moderate cytotoxicity against MCF-7 (IC50 = 10.4 μM). Compounds 1 and 6 showed weak cytotoxic activities against KB cell line with IC50 values of 29.3 and 24.7 μM, respectively.

Plants with anticancer properties are considered as cancer preventive and treatment sources, due to their some biological effects. Apoptosis induction and anti-proliferative effects of Baneh extract on various cancer cell lines have been reported. Hence, this study was designed to evaluate the cytotoxic effects of this fruit on KB and human gingival fibroblast cell lines (HGF). KB and HGF cells were treated with various concentrations of ethanolic Baneh extract and cisplatin as positive control. Cytotoxic activity and apoptosis induction were investigated using WST-1 and Annexin V assays. Data were analyzed using ANOVA and student's t-tests. IC50 after 24 and 48 hours treatment were respectively 2.6 and 1 mg/mL for KB cell line, and 1.5 and 1.6 mg/mL for HGF cell. During 48 hours Baneh extract induced apoptosis without significant necrosis, in a time- and dose-dependent manner. The induction of apoptosis in KB cells was significantly higher than HGF. It seems that ethanolic extract of Baneh contains compounds that can suppress KB cell growth through the induction of apoptosis. Within 48 hours, less cytotoxic effects were observed on normal fibroblast cells; therefore, it might be a potential anticancer agent.

Aim and Background: Oral squamous cell carcinoma (OSCC) is the 16th most common malignancy ranking worldwide. Among many types of cancer treatment, chemotherapy is the most common method. Major problems of treating OSCC with existing chemotherapeutic drugs are its adverse side effects and drug resistance. Anticancer properties present in fruits and vegetables might help to resolve these problems and prevent cancer. The purpose of the study is to assess the anticancer effect of watermelon and pumpkin seed extract on KB (OSCC) cell line. Materials and Methods: The KB cell line was grown in a minimal essential medium and maintained as monolayers in a culture plate. Citrullus lanatus (watermelon) and Cucurbita pepo (pumpkin) seed extracts from the fruit were extracted and subjected to Soxhlet extraction individually with organic solvent ethanol. 3-(4,5-Dimethylthiazol-2-yl)-2,5- Diphenyltetrazolium Bromide) (MTT) test was used to analyze the anticancer effect of the extracts on KB cell line. Results: The comparison between the average cell viability of pumpkin and watermelon seed extract showed a significant difference in cytotoxicity. The mean cell viability of pumpkin seed extract was 30.27%, while for the watermelon seed extract, it was higher at 42.70%, indicating that pumpkin seed extract was more cytotoxic than watermelon seed extract. Conclusion: Watermelon and pumpkin seeds have various properties such as anti-inflammatory, antioxidant, antibacterial, and anticancer effect. This study evaluated the anticancer property of pumpkin and watermelon seed extracts and indicated that as the concentration of the extract increases, the cell viability gradually decreases.

Cytotoxicity against KB and NCI-H187 cell lines of modified flavonoids from Kaempferia parviflora

o-Aminophenol derivatives are of particular interest for their diverse biological activities and potential therapeutic applications. Such as, antioxidant, antibacterial, and cytotoxic activities. This study aimed to design and synthesize a series of novel o-aminophenol derivatives through an efficient multi-step process, characterize them using modern spectroscopic techniques, and evaluate their antimicrobial, antioxidant, and cytotoxic activities. A series of novel derivatives of o-aminophenol have been successfully synthesized with very high efficiency through a simple six-step process using readily available chemicals and straightforward reactions. The structures of all products were accurately determined using modern spectroscopic methods such as 1D and 2D NMR, as well as IR, MS spectroscopy, and X-ray methods. The antimicrobial activities of eight o-nitrophenol derivatives were assessed against Gram (-) and Gram (+) bacteria as well as fungi. In comparison, antioxidant activities were tested for two o-nitrophenol and 11 o-aminophenol derivatives using SC50 and EC50 assays. Cytotoxicity was evaluated on KB, HepG2, A549, and MCF7 cancer cell lines. Six synthesized compounds 5b, 5c, 5g, 6b, 6c, 6g exhibited unusual doublet signals in the H8 region of the 1H NMR spectrum, attributed to atropisomer formation. Eight o-nitrophenol derivatives demonstrated weak antimicrobial activity, with MIC values ranging from 100 to 200 μg/mL. Compound 5g showed activity against all tested bacterial and fungal strains. In antioxidant testing, eight o-aminophenol derivatives 6a, 6b, 6c, 6e, 6f, 6h, 6i, and 12b displayed excellent activity, with SC50 values between 18.95 and 34.26 μg/mL, approaching ascorbic acid's SC50 value of 12.60 μg/mL. Three derivatives 6d, 6g, and 12a showed superior antioxidant activity with EC50 values between 4.00 and 11.25 μg/mL, surpassing quercetin's standard of 9.8 μg/mL. Cytotoxicity assays revealed that oaminophenol derivatives 6b, 6c, 6f, 6i, and 12b exhibited moderate inhibitory effects on KB cell lines with IC50 values from 32 to 74.94 μg/mL. Compound 6i demonstrated moderate cytotoxic activity against HepG2, A549, and MCF7 cell lines, with IC50 values of 29.46, 71.29, and 80.02 μg/mL, respectively. Design, synthesis, antimicrobial activity, DPPH Radical Scavenging, Cytotoxic activity, Evaluation of H8 signal anomalies in certain compounds, and Single crystal X-ray diffraction analysis.

A new flavanol derivative, (2R,3R)-3-acetoxy-7-hydroxy-3′,4′-methylenedioxyflavan (1), was co-isolated from the rhizomes of Zephyranthes ajax Hort. with the following seven known compounds: 7-hydroxyflavan (2), 7,4′-dihydroxyflavan (3), 7,4′-dihydroxy-8-methylflavan (4), 7,3′-dihydroxy-4′-methoxyflavan (5), 5,4′-dihydroxy-7-methoxy-6-methylflavan (6), 7-hydroxy-3′,4′-methylenedioxyflavanone (7) and haemanthamine (8). Their structures were elucidated by combining 1D-/2D-NMR, CD, UV and HRESIMS data, and comparisons with reported data in literature were made. Among these known compounds, 2, 3, 4, 6 and 7 were isolated from the genus Zephyranthes for the first time. In addition, the cytotoxicity assay indicated that compound 8 has potent cytotoxic activity against human hepatocellular carcinoma (the HepG2 cell line), human lung carcinoma (the SK-LU-1 cell line), human carcinoma in the mouth (the KB cell line), human colon carcinoma (the SW480 cell line) and human stomach gastric adenocarcinoma (the AGS cell line), with IC50 values ranging from 4.4 to 11.3 µM. This is the first study reporting the cytotoxicity of compound 8 against the SK-LU-1 cancer cell lines.

Paxiiones A–D, four new flavonoids from the stem of Mallotus paxii Pamp.