Isolation of diverse bioactive compounds from Euphorbia balsamifera: Cytotoxicity and antibacterial activity studies

Antibacterial and cytotoxic activities of Euphorbia balsamifera, fractions and pure compounds were evaluated. The cytotoxic assays for HCT116, HePG2 and MCF7 showed a significant IC₅₀: 54.7 and 76.2 µg/mL of non-polar fraction “n-hexane” against HCT116 and HePG2, respectively. Antibacterial results revealed that plant fractions exhibited significant potential against the tested pathogens than the total extract where n-butanol and ethyl acetate fractions showed significant antibacterial activity (P < 0.05) against tested bacterial strains. Isolation and structure determination of compounds from n-hexane and n-butanol fractions were performed. From n-hexane fraction, 29-nor-cycloartanol (1), lanost-8-en-3-ol (2a), cycloartanol (2b) and kampferol-3,4'-dimethyl ether (3) were isolated and structurally identified, along with 24 compounds were tentatively identified by GC–MS. From the polar n-butanol fraction, 4-O-β-D-glucopyranosyl-2-hydroxy-6-methoxyacetophenone (4), 4-O-α-L-rhamnosyl-(1 → 6)-β-D-glucopyranosyl-2-hydroxy-6methoxy-acetophenone (5), quercetin-3-O-glucopyranoside (6) and isoorientin (7) were assigned. Structures of the obtained compounds were determined by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. Except compounds 1 and 5, all reported compounds announced antibacterial efficiency. Compound 2 showed selectively the highest activity against Enterococcus faecalis (22 ± 0.13 mm), meanwhile 4-O-β-D-glucopyranosyl-2-hydroxy-6-methoxyacetophenone (4) showed broadly the highest antibacterial activity with MIC of 1.15–1.88 mg/mL against the test Gram-positive and Gram-negative bacteria. Cytotoxic assays indicated that kampferol-3,4'-dimethyl ether (3) exhibited the highest activity with matching IC₅₀ values to doxorubicin; 111.46, 42.67 and 44.90 µM against HCT116, HePG2 and MCF7, respectively, however, it is toxic on retina normal cell line RPE1.     

C19-Diterpenoid alkaloids from Aconitum richardsonianum

Three new aconitine-type C₁₉-diterpenoid alkaloids, richardsonines A-C (1–3), were isolated from the roots of Aconitum richardsonianum Lauener, together with seventeen known compounds (4–20). Their structures were elucidated by extensive spectroscopic analysis, and the absolute stereochemistry of 1 was confirmed by X-ray crystallography. Compounds 2, 5, 8 and 9 were rare C₁₉-diterpenoid alkaloids bearing an OH group at C-16. Isolated compounds were evaluated for inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated neuroinflammatory responses in BV-2 microglial cells. Compounds 3 and 7 showed weak antineuroinflammatory effects with inhibition rates of 35.32 ± 2.29% and 39.94 ± 2.50%, respectively, at a concentration of 100 µM.     

Chemical constituents from Abrus cantoniensis and their cytotoxic effects on cancer cells

Two new compounds named 4-(4-hydroxybenzyl)-isofraxidin (1) and 1''-methoxyl-bavacoumestan B (2), along with five known compounds (3–7) were isolated from the EtOAc-soluble extract of Abrus cantoniensis. Their structures were elucidated with spectroscopic and physico-chemical analyses. All isolates were evaluated for their cytotoxic activities against four cancer cell lines including HepG2, SMMC-7721, A549 and MCF-7. Among them, compounds 1 and 5 exhibited significant cytotoxic activity on the above four cell lines. In particular, 1 showed the potent cytotoxic activity on HepG2 and SMMC-7721 cells with IC₅₀ values of 4.31 ± 0.5 and 3.24 ± 0.9 μM, respectively.     

Three new 2-(2-phenylethyl)chromones from ‘Chong-lou’ agarwood of Aquilaria sinensis

Three new 2-(2-phenylethyl)chromones (1, 2 and 3), together with four known analogues 4~7 were isolated from ‘Chong-lou’ agarwood originating from Aquilaria sinensis for the first time. Their new structures were elucidated on the basis of spectroscopic techniques (UV, IR, MS, 1D and 2D NMR), as well as by comparison with the literature data. Compounds 6 and 7 exhibited significant cytotoxicity against human cancer cell line K562 with IC₅₀ values of 19.79 ± 0.03 and 21.39 ± 0.05 μM, respectively.     

Design,synthesis, docking study, α-glucosidase inhibition,and cytotoxic activities of acridine linked to thioacetamides as novel agents in treatment of type 2 diabetes

A novel series of acridine linked to thioacetamides 9a–o were synthesized and evaluated for their α-glucosidase inhibitory and cytotoxic activities. All the synthesized compounds exhibited excellent α-glucosidase inhibitory activity in the range of IC₅₀ = 80.0 ± 2.0–383.1 ± 2.0 µM against yeast α-glucosidase, when compared to the standard drug acarbose (IC₅₀ = 750.0 ± 1.5 µM). Among the synthesized compounds, 2-((6-chloro-2-methoxyacridin-9-yl)thio)-N-(p-tolyl) acetamide 9b displayed the highest α-glucosidase inhibitory activity (IC₅₀ = 80.0 ± 2.0 μM). The in vitro cytotoxic assay of compounds 9a–o against MCF-7 cell line revealed that only the compounds 9d, 9c, and 9n exhibited cytotoxic activity. Cytotoxic compounds 9d, 9c, and 9n did not show cytotoxic activity against the normal human cell lines HDF. Kinetic study revealed that the most potent compound 9b is a competitive inhibitor with a K_i of 85 μM. Furthermore, the interaction modes of the most potent compounds 9b and 9f with α-glucosidase were evaluated through the molecular docking studies.     

Synthesis and in vitro anticancer evaluation of some fused indazoles,quinazolines and quinolines as potential EGFR inhibitors

derivatives of benzo[g]indazole 5a, b, benzo[h]quinazoline 7, 12a-c, 13a-c and 15a-c and benzo[h]quinoline 17a-c and 19a-c were synthesized from 6-methoxy-3,4-dihydronaphthalen-1(2H)-one (1). Anticancer activity of all the synthesized compounds was evaluated against four cancerous cell lines; HepG2, MCF-7, HCT116 and Caco-2. MCF-7 cells emerged as the most sensitive cell line against the target compounds. All the examined compounds, except 5a and 5b, displayed potent to moderate anticancer activity against MCF-7 cells with an IC₅₀ values ranging from 7.21 to 21.55 µM. In particular, compounds 15c and 19b emerged as the most potent derivatives against EGFR-expressing MCF-7 cells with IC₅₀ values = 7.70 ± 0.39 and 7.21 ± 0.43 μM, respectively. Additionally, both compounds did not display any significant cytotoxicity towards normal BHK-21 fibroblast cells (IC₅₀ value > 200 µM), thereby providing a good safety profile as anticancer agents. Furthermore, compounds 15c and 19b displayed potent inhibitory activity towards EGFR in the sub-micromolar range (IC₅₀ = 0.13 ± 0.01 and 0.14 ± 0.01 μM, respectively), compared to that of Erlotinib (IC₅₀ = 0.11 ± 0.01 μM). Docking studies for 15c and 19b into EGFR active site was carried out to explore their potential binding modes. Therefore, compounds 15c and 19b can be considered as interesting candidates for further development of more potent anticancer agents.     

Cytotoxic terpenoids from the stem bark of Taxus wallichiana

Chemical study of the stem bark of Taxus wallichiana Zucc. afforded the isolation of two new cyclopenta[b]naphthalene terpenoids, wallichianones A (1) and B (2) and 13 taxane diterpenoids, baccatin III (3), 10-deacetylbaccatin III (4), baccatin IV (5), 1-dehydroxybaccatin IV (6), 1-deoxybaccatin VI (7), taxol (8), 10-deacetyltaxol (9), 7-epi-10-deacetyltaxol (10), taxol-7-xyloside (11), 7-xylosyl-10-deacetyltaxol C (12), cephalomannine (13), 10-deacetylcaphalomannine (14), and 7-epi-10-deacetylcephalomannine (15). Their structures were identified by comprehensive analyses of the spectroscopic methods, including NMR and mass spectra. The absolute configurations of 1 and 2 were clarified by time-dependent density functional theory (TD-DFT) electronic circular dichroism (ECD) spectroscopic analyses. Compounds 3 and 7–15 showed cytotoxicity against all five human cancer cell lines, including lung (SK-LU-1), liver (HepG2), breast (MCF7), skin (SK-Mel-2), and prostate (LNCaP), with IC₅₀ values ranging from 1.4 ± 0.2 to 88.1 ± 5.8 μM. Compounds 9–11, 14, and 15 were additionally cytotoxic against human embryonic kidney (HEK-293A) cell line (IC₅₀ = 14.5 ± 1.0–48.4 ± 1.0 μM), however, 13 was noncytotoxic toward this cell line. The positive control, ellipticine showed cytotoxicity against all the cell lines, with IC₅₀ values in a range of 1.5 ± 0.1–2.0 ± 0.3 μM. Preliminary analysis of the structural and cytotoxicity relationship of compounds 3–15 suggested that the phenylalanine substituent at C-13 may contribute an important role for the cytotoxicity of the taxane diterpenoids.     

New coumestan and coumaronochromone derivatives from Dalbergia boehmii Taub. (Fabaceae)

Chemical investigation of leaves and heartwood of Dalbergia boehmii resulted in the isolation of two new phenolic compounds, designated dalbergestan (1) and dalbergichromone (2), along with eleven known compounds, carpachromene (3), proanthocyanidin A-2 (4); piceatannol (5); biochanin A (6); macckiain (7); homopterocarpin (8); angolensin (9); medicarpin (10); 2′,7-dihydroxy-4′,5′-dimethoxyisoflavone (11); 2′-methoxyformononetin (12); and genistein (13). The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses including, IR, UV, 1D and 2D – NMR as well as HRMS data. Some of the isolated compounds were evaluated for their in vitro insulin secretion activity on isolated mice islets, leishmanicidal activity against L. major (DESTO) promastigotes and in vitro cytotoxicity on MCF-7 cell lines. All tested compounds were inactive on glucose-stimulated insulin secretion at stimulatory glucose (20.0 mM) from MIN6 cells. Compounds 3 (IC₅₀, 70.0 μg/ml), 6 (IC₅₀, 60.3 μg/ml), 7 (IC₅₀, 86.5 μg/ml) and 13 (IC₅₀, 62.6 μg/ml) exhibited low leishmanicidal activity while compound 12 (IC₅₀, 56.8 μg/ml) displayed a moderate activity. Compounds 3 and 5 were found to be active against MCF-7 at 50 μM with IC₅₀ value 33.2 ± 3.79 μg/ml and 42.64 ± 5.05 μg/ml respectively.     

Spirostanols from the roots and rhizomes of Trillium tschonoskii

Two novel spirostanols, (23S,24R,25S)-18-norspirost-1,4,13-triene-21,23,24-triol-3,15-dione (1) and (23S,24S,25S)-spirost-5-ene-1β,3β,21,23,24-pentaol (2), a new natural product (3), and two known analogues (4 and 5) were isolated from the ethyl acetate-soluble portion of the ethanolic extract of Trillium tschonoskii Maxim. Their structures were elucidated by extensive spectroscopic analyses, and their cytotoxic activities on four kinds of human tumor cells were studied in vitro. Compound 4 showed significant cytotoxic activity against MCF-7 and A549 with IC₅₀ values of 6.16 ± 2.21 and 28.5 ± 11.5 μM, respectively, while 5 exhibited selective cytotoxicity against A549 with an IC₅₀ value of 13.0 ± 4.51 μM.     

New carbazole linked 1,2,3-triazoles as highly potent non-sugar α-glucosidase inhibitors

In the present study, a series of new carbazole linked 1H-1,2,3-triazoles (2–27) were synthesized via click reaction of N-propargyl-9H-carbazole (1) and azides of appropriate acetophenones and heterocycles. Synthesized carbazole triazoles including 7, 9, 10, 19, 20, and 23–26 (IC₅₀ = 0.8 ± 0.01–100.8 ± 3.6 μM), exhibited several folds more potent α-glucosidase inhibitory in vitro activity as compared to standard drug, acarbose. Compounds 2–5, 7–13, and 17–27 did not show any cytotoxicity against 3T3 cell lines, except triazoles 6, and 14–16. Among the series, carbazole triazoles 23 (IC₅₀ = 1.0 ± 0.057 μM) and 25 (IC₅₀ = 0.8 ± 0.01 μM) were found to be most active, and could serve as an attractive building block in the search of new non-sugar derivatives as anti-diabetic agents.     

A new megastigmane from Kalanchoe tubiflora (Harvey) Hamet

One new megastigmane, (6S,7R,8R,9S)-6-oxaspiro-7,8-dihydroxymegastigman-4-en-3-one (1) (tubiflorone, 1), and ten known compounds were isolated and characterized from the EtOH extract of Kalanchoe tubiflora (Harvey) Hamet. Structures of these isolates were assigned based on spectroscopic analyses that included 1D and 2D NMR techniques, such as HMQC, HMBC, and NOESY. The anti-inflammatory activities of selected isolated compounds (1–6 and 9–11) were evaluated as inhibitory activities against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 cell lines. Compounds 1–4, 6, 9, and 11 possessed nitric oxide inhibitory activity with IC₅₀ values ranging from 15.1 ± 0.9 to 98.9 ± 1.3 μM.     

New bioactive derivatives of nonactic acid from the marine Streptomyces griseus derived from the plant Salicornia sp.

Three new compounds, butyl homononactate (5), butyl nonactate (6), 8-actyl homononactic acid (7), along with four known compounds homononactic acids (1), nonactic acid (2), homononactyl nonactate (3), homononactyl homononactate (4) were isolated from the marine Streptomyces griseus RSH0407, derived from the plant Salicornia sp., Chenopodiaceae. Their structures were elucidated by extensive spectroscopic techniques and by comparison with data reported in the literature. The absolute configuration of 3 was first reported by using X-ray copper radiation. Compound 5 exhibited cytotoxic activities against the HCT-8, A2780, BGC-823, BEL-7402, and A549 cell lines in vitro, with IC₅₀ values of 2.87 ± 0.20, 4.90 ± 0.30, 2.19 ± 0.32, 5.07 ± 0.23 and 1.78 ± 0.18 μM, respectively, and compounds 4–7 showed weak antibacterial activities against four bacterials respectively.     

Anti-inflammatory components of Euphorbia humifusa Willd.

Two new compounds, euphorbinoside (1) and dehydropicrorhiza acid methyl diester (2), along with 24 known compounds (3–26) were isolated from Euphorbia humifusa Willd. The effects of these compounds on soluble epoxide hydrolase (sEH) inhibitory activity were evaluated. Flavonoid compounds (10–21) exhibited high sEH inhibitory activity. Among them, compounds 12, 13, and 19 greatly inhibited sEH enzymatic activity, with IC₅₀ values as low as 18.05 ± 1.17, 18.64 ± 1.83, and 17.23 ± 0.84 μM, respectively. In addition, the effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) production by RAW 264.7 cells were investigated. Compounds 3–6, 8, 18, 20–23, and 25–26 inhibited the production of both NO and TNF-α, with IC₅₀ values ranging from 11.1 ± 0.9 to 45.3 ± 1.6 μM and 14.4 ± 0.5 to 44.5 ± 1.2 μM, respectively.     

Design and synthesis of C3-tethered 1,2,3-triazolo-β-carboline derivatives: Anticancer activity,DNA-binding ability,viscosity and molecular modeling studies

A series of new DNA-interactive C3-tethered 1,2,3-triazolo-β-carboline derivatives have been synthesized via ‘click’ reaction and evaluated for their in vitro cytotoxicity as well as DNA binding affinity. Interestingly, these hybrids have displayed potent in vitro cytotoxicity in comparison to Harmine against the HT-29 (colon cancer) and HGC-27 (gastric cancer) cell lines. The compounds 7f, 7k, 7n and 7s appear to be more effective against the HGC-27 cell line, among which compound 7f showed the highest cytotoxicity (5.44 ± 0.58, IC₅₀ μM). The compounds 7e and 7f appear to be more active against the HT-29 cell line, among which compound 7f exhibited the highest cytotoxicity (3.67 ± 0.62, IC₅₀ μM). To gain more insight into the DNA-binding ability, spectroscopic techniques such as UV–Visible, fluorescence and circular dichroism studies were performed. Viscosity measurements and molecular docking studies substantiate that these compounds indeed bind to DNA via the minor groove.     

Synthesis and β-glucuronidase inhibitory activity of 2-arylquinazolin-4(3H)-ones

2-Arylquinazolin-4(3H)-ones 1–25 were synthesized by reacting anthranilamide with various benzaldehydes using CuCl₂·2H₂O as a catalyst in ethanol under reflux. Synthetic 2-arylquinazolin-4(3H)-ones 1–25 were evaluated for their β-glucuronidase inhibitory potential. A trend of inhibition IC₅₀ against the enzyme in the range of 0.6–198.2 μM, was observed and compared with the standard d-saccharic acid 1,4-lactone (IC₅₀ = 45.75 ± 2.16 μM). Compounds 13, 19, 4, 12, 14, 22, 23, 25, 15, 8, 17, 11, 21, 1, 3, 18, 9, 2, and 24 with the IC₅₀ values within the range of 0.6–44.0 μM, indicated that the compounds have superior activity than the standard. The compounds showed no cytotoxic effects against PC-3 cells. A structure–activity relationship is established.     

Ellagitannin and flavonoid constituents from Agrimonia pilosa Ledeb. with their protein tyrosine phosphatase and acetylcholinesterase inhibitory activities

A new ellagitannin, agritannin (1), a new flavone glycoside, agriflavone (2), and another flavone glycoside with spectroscopic data reported for the first time, kaempferol-3-O-[(S)-3-hydroxy-3-methylglutaryl (1→6)]-β-d-glucoside (3), along with 16 known compounds were isolated from the aerial parts of Agrimonia pilosa Ledeb. These compounds were evaluated for PTP1B inhibitory activity. Among them, compounds 9 and 18 displayed potential inhibitory activity against PTP1B with IC₅₀ values of 7.14 ± 1.75 and 7.73 ± 0.24 μM, respectively. In addition, compound 1 showed significant inhibitory effect with an IC₅₀ value of 17.03 ± 0.09 μM. Furthermore, these compounds were tested in AChE inhibitory assays. Most of them were found to have moderate inhibitory effects, with IC₅₀ values ranging from 60.20 ± 1.09 to 92.85 ± 1.12 μM. Except compounds 3, 8, and 18 were inactive.     

Investigations of antiproliferative and antioxidant activity of β-lactam morpholino-1,3,5-triazine hybrids

This article reports for the first time the synthesis of some novel β-lactam morpholino-1,3,5-triazine hybrids by a [2+2]-cycloaddition reaction of imines 7a–c, 9a–c and 11 with ketenes derived from substituted acetic acids. The reaction was totally diastereoselective, leading exclusively to the formation of cis-β-lactams 8a–l, 10a–f and 12a–c. The synthesized compounds were tested for activity towards SW1116, MCF-7 and HepG2 cancer cell lines and non-cancerous HEK-293 cell line by MTT assay. None of the compounds exert an observable effect on HepG2, MCF-7 and HEK-293 cells, but compounds 7b, 8f, 8g, 8l, 10c, and 10e exhibited excellent growth inhibitory activity (IC₅₀ < 5 µM) against SW 1116 cells, comparable to that of doxorubicin (IC₅₀ = 6.9 µM). An evaluation of the antioxidant potential of each of the compounds, performed by diphenylpicrylhydrazyl (DPPH) assay, indicated that 7b, 9a, 9b and 9c have strong free radical scavenging activity. UV absorption titration studies reveal that 7b, 8l, 8g and 8f interact strongly with calf-thymus DNA (CT-DNA) in the order of 8l > 7b > 8f > 8g. Collectively, the in vitro capabilities of some of these morpholino-triazine imines and β-lactams suggest possible applications to development of new antioxidants and DNA binding therapeutics.     

Aldose reductase inhibition of a saponin-rich fraction and new furostanol saponin derivatives from Balanites aegyptiaca

BackgroundBalanites aegyptiaca Del. (Zygophyllaceae) fruits are used to treat hyperglycemia in Egyptian folk medicine and are sold by herbalists in the Egyptian open market for this purpose. Nevertheless, the fruits have not yet been incorporated into pharmaceutical dosage forms. The identity of the bioactive compounds and their possible mechanisms of action were not well understood until now.PurposeAldose reductase inhibitors are considered vital therapeutic and preventive agents to address complications caused by hyperglycemia. The present study was carried out to identify the primary compounds responsible for the aldose reductase inhibitory activity of Balanites aegyptiaca fruits.Study designThe 70% ethanolic extract of Balanites aegyptiaca fruit mesocarp and its fractions were screened for inhibition of the aldose reductase enzyme. Bio-guided fractionation of the active butanol fraction was performed and the primary compounds present in the saponin-rich fraction (D), which were responsible for the inhibitory activity, were characterized. HPLC chromatographic profiles were established for the different fractions, using the isolated compounds as biomarkers.MethodsAldose reductase inhibition was tested in vitro on rat liver homogenate. The butanol fraction of the 70% ethanolic extract was fractionated using vacuum liquid chromatography (VLC, RP-18 column). The most active sub-fraction D, which was eluted with 75% methanol, was subjected to preparative HPLC to isolate the bioactive compounds.ResultsThe butanol fraction displayed inhibitory activity against the aldose reductase enzyme (IC₅₀ = 55.0 ± 6 µg/ml). Sub-fraction D exhibited the highest inhibitory activity (IC₅₀ = 12.8 ± 1 µg/ml). Five new steroidal saponin derivatives were isolated from this fraction. The isolated compounds were identified as compound 1a/b, a 7:3 mixture of the 25R:25S epimers of 26-O-β-D-glucopyranosyl-furost-5-ene-3,22,26-triol 3-O-[α-L-rhamnopyranosyl-(1→3)- β-D-glucopyranosyl-(1→2)]- α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside; compound 2, 26-O-β-D-glucopyranosyl-(25R)-furost-5-ene-3,22,26-triol 3-O-[ β-D-glucopyranosyl-(1→2)]- α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside; compound 3, 26-O-β-D-glucopyranosyl-(25R)-furost-5,20-diene-3,26-diol 3-O-[α-L-rhamnopyranosyl-(1→3)- β-D-glucopyranosyl-(1→2)]- α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside; compound 4, 26-O-β-D-glucopyranosyl-(25R)-furost-5,20-diene-3,26-diol 3-O-[ β-D-glucopyranosyl-(1→2)]- α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside; and compound 5, which is the 25S epimer of compound 4, by using various spectroscopic methods [MS,1D and 2D NMR (HSQC, HMBC, DQF-COSY, HSQC-TOCSY)]. Compounds 1a/b, 2, 3, 4, 5 exhibited highly significant aldose reductase inhibitory activities (IC₅₀ values were 1.9 ± 0.2, 1.3 ± 0.5, 5.6 ± 0.2, 5.1 ± 0.4, 5.1 ± 0.6 µM, respectively) as compared to the activity of the reference standard quercetin (IC₅₀ = 6.6 ± 0.3 µM).ConclusionThe aldose reductase inhibitory activity of Balanites fruits is due to the steroidal saponins present. HPLC chromatographic profiles of the crude butanol fraction and its 4 sub-fractions showed that the most highly bioactive fraction D contained the highest amount of steroidal saponins (75%) as compared to the 21% present in the original butanol fraction. The isolated furostanol saponins proved to be highly active in an in vitro assay.     

Xylarianins A-D from the endophytic fungus Xylaria sp. SYPF 8246 as natural inhibitors of human carboxylesterase 2

Eighteen secondary metabolites were isolated from the fermentation broth of the endophytic fungus Xylaria sp. SYPF 8246, including four new compounds, xylarianins A-D (1–4), three new natural products, 6-methoxycarbonyl-2′-methyl-3,5,4′,6′-tetramethoxy-diphenyl ether (5), 2-chlor-6-methoxycarbonyl-2′-rnethyl-3,5,4′,6′-tetramethoxy-diphenyl ether (6), and 2-chlor-4′-hydroxy-6-methoxy carbonyl-2′-methyl-3,5,6′-trimethoxy-diphenyl ether (7), and eleven known compounds (8–18). Their structural elucidations were conducted by using 1D and 2D NMR, HRESIMS, and Rh₂(OCOCF₃)₄-induced electronic circular dichroism (ECD) spectra analyses. The integrated ¹H and ¹³C NMR data of three new natural products 5–7 were reported for the first time. All the isolated compounds were assayed for their inhibitory activities against human carboxylesterase 2 (hCE 2). Compounds 1, 5–9, and 18 displayed significant inhibitory activities against hCE 2 with IC₅₀ values of 10.43 ± 0.51, 6.69 ± 0.85, 12.36 ± 1.27, 18.25 ± 1.78, 29.78 ± 0.48, 18.86 ± 1.87, and 20.72 ± 1.51 µM, respectively. The interactions between compounds 1 and 5 with hCE 2 were anaylzed by molecular docking.     

Facile synthesis of novel substituted aryl-thiazole (SAT) analogs via one-pot multi-component reaction as potent cytotoxic agents against cancer cell lines

In this study, twenty-five (25) substituted aryl thiazoles (SAT) 1–25 were synthesized, and their in vitro cytotoxicity was evaluated against four cancer cell lines, MCF-7 (ER^+ve breast), MDA-MB-231 (ER^−ve breast), HCT116 (colorectal) and HeLa (cervical). The activity was compared with the standard anticancer drug doxorubicin (IC₅₀ = 1.56 ± 0.05 μM). Among them, compounds 1, 4–8, and 19 were found to be toxic to all four cancer cell lines (IC₅₀ values 5.37 ± 0.56–46.72 ± 1.80 μM). Compound 20 was selectively active against MCF7 breast cancer cells with IC₅₀ of 40.21 ± 4.15 μM, whereas compound 19 was active against MCF7 and HeLa cells with IC₅₀ of 46.72 ± 1.8, and 19.86 ± 0.11 μM, respectively. These results suggest that substituted aryl thiazoles 1 and 4 deserve to be further investigated in vivo as anticancer leads.