Two new bioactive triterpenoids from the roots of Colubrina asiatica

Abstract

Two new ceanothane triterpenes, 3,7-O,O-dibenzoyl ceanothic acid methylester (1) and 3-O-acetyl-7-O-benzoyl ceanothic acid methylester (2), along with nine known compounds (3–11), were isolated from the roots of Colubrina asiatica. The isolated compounds were identified by spectroscopic evidence. Compounds 1 and 2 showed antimalarial activity against Plasmodium falciparum with IC₅₀ values of 4.67 and 3.07?µg/mL, respectively. Compound 2 also showed antimycobacterial activity against Mycobacterium tuberculosis (MIC 6.25?µg/mL). In addition, compounds 1, 2, 10 and 11 showed cytotoxicity against three cancer cell lines (KB, NCI-H187 and MCF-7) with IC₅₀ values ranging from 8.32 to 46.72?µg/mL.     

New p-terphenyl and benzoquinone metabolites from the bioluminescent mushroom Neonothopanus nambi

Abstract

Two new p-terphenyls, neonambiterphenyls A and B (1–2), a new benzoquinone, neonambiquinone A (3), together with six known sesquiterpenes (4–9), were isolated from the bioluminescent mushroom Neonothopanus nambi PW3. The isolated compounds were identified by mass, IR and spectroscopic analyses (1D and 2D NMR). Compounds 1–3 and 5–7 showed cytotoxicity against cancer cell lines such as KB, NCI-H187 and MCF-7 with IC₅₀ values ranging from 1.45 to 49.31?µg/mL. In addition, compounds 1 and 5 showed cytotoxicity against Vero cells with IC₅₀ values of 38.72 and 32.90?µg/mL, respectively.     

Anti-inflammatory activity of saponins from roots of Impatiens parviflora DC.

Abstract

Two triterpene saponins (IPS-1, IPS-2) for the first time were isolated from the roots of Impatiens parviflora DC. (Balsaminaceae). Their anti-inflammatory activity was evaluated by means of two in vitro models: anti-hyaluronidase and anti-denaturation assays. Both saponins were shown to be potent hyaluronidase inhibitors that affect the enzyme in a dose-dependent manner. The anti-hyaluronidase effect of IPS-2 (IC₅₀?=?286.7?µg/mL) was higher than that of the reference drug: escin (IC₅₀?=?303.93?µg/mL). Both saponins protected bovine serum albumin from heat-induced denaturation in a dose-dependent manner. IPS-1 demonstrated higher anti-denaturation effect (IC₅₀?=?86.7?µg/ml) than IPS-2 (IC₅₀?=?109.76?µg/mL) or the standard drug: acetylsalicylic acid (IC₅₀?=?262.22?µg/mL). In conclusion, potent activity of IPS-1, IPS-2 in both in vitro assays shows that saponins from I. parviflora have anti-inflammatory activity. The obtained results allow to suggest that such compounds may be beneficial in inflammatory conditions, especially associated with excessive degradation of hyaluronic acid.     

Penicindopene A,a new indole diterpene from the deep-sea fungus Penicillium sp. YPCMAC1

A new indole diterpene, named penicindopene A (1), together with seven known compounds (2?–?8), was isolated from the deep-sea fungus Penicillium sp. YPCMAC1. The structure of penicindopene A was elucidated by extensive spectroscopic analyses (1?D and 2?D NMR, and HRESIMS data), in addition to the ECD calculations for the assignments of its absolute configuration. Penicindopene A represented the first example of indole diterpenes possessing a 3-hydroxyl-2-indolone moiety, and it exhibited moderate cytotoxicities against A549 and HeLa cell lines with IC₅₀ values of 15.2 and 20.5?µM, respectively.     

Antiglycation,antioxidant, and cytotoxic activities of Uvaria chamae root and essential oil composition

Abstract

Uvaria chamae (Annonaceae), is an essential oil bearing plant; the root is acclaimed as an effective remedy for folkloric diabetic therapy. The root extracts were evaluated for composition, antiglycation, antioxidant, and cytotoxicity. Flavonoids, cardiac glycosides, and tannins were relatively high in the alcohol extract; benzyl benzoate (23.3%), dimethoxy-p-cymene (14.2%), τ-cadinol (12.1%), and methyl thymol (8.7%) predominated the constituents identified by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The ethanol extract demonstrated significant antiglycation activity (IC₅₀, 1.12?mg/mL), and cytotoxicity to brine shrimp (LC₅₀, 25.01?µg/mL). The extract (IC₅₀, 8.0?µg/mL; absorbance 0.531, 100?µg/mL) also exhibited better antioxidant effects compared with the essential oil (IC₅₀, 50.0?µg/mL; absorbance 0.292, 100?µg/mL) using 2,2-diphenyl-1-picrylhydrazyl radical and ferric reducing power assays respectively. U. chamae root possess antiglycation effect, and may also reduce oxidative stress in patients with diabetes; its antiglycation effect, oil composition, and cytotoxicity are reported for the first time.

     

Carbazole-pyranocoumarin conjugate and two carbazole alkaloids from the stems of Clausena excavata

A carbazole-pyranocoumarin conjugate, carbazomarin B (1), and two carbazole alkaloids, 6-methoxymukonidine (2) and 2-hydroxy-3-methoxycarbazole (3), together with 27 known compounds (4–30), were isolated from the stems of Clausena excavata. Their structures have been elucidated by spectroscopic analyses. Compound 2 showed moderate cytotoxicity to HuCCA-1, MOLT-3 and HepG2 cancer cell lines with IC₅₀ values of 15.09–28.50 μg/mL, but none to A549 cell line. Heptaphylline (6) and nordentatin (23) were found to show moderate cytotoxic activity against HepG2 cell line with IC₅₀ values of 12.33 and 11.33, respectively, while clausine K (27) exhibited strong cytotoxicity with IC₅₀ value of 1.05 μg/mL, better than a standard drug (etoposide, IC₅₀ 13.40 μg/mL).     

Design and synthesis of fluorescent symmetric bis-triazolylated-1,4-dihydropyridines as potent antibreast cancer agents

Herein, we report the synthesis of fluorescent 1,4-dihydropyridine-linked bis-triazoles (2a–2n) through Hantzsch synthesis by the condensation of o/m-chloro-substituted benzaldehyde, ethyl 3-oxo-4(prop-2-yn-1-yloxy)butanoate, and ammonium acetate in the presence of Ba(NO₃)₂ as a catalyst followed by the click reaction of resultant Hantzsch product (1) with various aromatic as well as aliphatic azides. All the synthesized compounds were well characterized by ¹H-NMR, ¹³C-NMR, FTIR, and HRMS spectral techniques. Antibreast cancer evaluation of all the synthesized derivatives revealed that the compounds 2f (IC₅₀?=?7?±?0.02?µM) and 2g (IC₅₀?=?5?±?0.03?µM) showed better anticancer activity (lower IC₅₀) than the standard drug tamoxifen (IC₅₀?=?11.2?±?0.01?µM) against breast carcinoma (MDA-MB-231) cell line. The synthesized compounds were also screened against normal human embryonic kidney (HEK-293) cell line and found to be nontoxic. The fluorescent nature and cytotoxicity assay of these newly synthesized hybrids recommend their utility in tumor cell imaging.     

In vitro cytotoxicity evaluation of thiourea derivatives bearing Salix sp. constituent against HK-1 cell lines

Abstract

In searching for drugs from natural product scaffolds has gained interest among researchers. In this study, a series of twelve halogenated thiourea (ATX 1-12) via chemical modification of aspirin (a natural product derivative) and evaluated for cytotoxic activity against nasopharyngeal carcinoma (NPC) cell lines, HK-1 via MTS-based colorimetric assay. The cytotoxicity studies demonstrated that halogens at meta position of ATX showed promising activity against HK-1 cells (IC₅₀ value ≤15?µM) in comparison to cisplatin, a positive cytotoxic drug (IC₅₀ value =8.9?±?1.9?µM). ATX 11, bearing iodine at meta position, showed robust cytotoxicity against HK-1 cells with an IC₅₀ value of 4.7?±?0.7?µM. Molecular docking interactions between ATX 11 and cyclooxygenase-2 demonstrated a robust binding affinity value of ?8.1?kcal/mol as compared to aspirin’s binding affinity value of ?6.4?kcal/mol. The findings represent a promising lead molecule from natural product with excellent cytotoxic activity against NPC cell lines.     

Atalantums H-K from the peels of Atalantia monophylla and their cytotoxicity

Abstract

Four new benzoyltyramines, atalantums H-K (1–4) and seven known compounds were isolated from the peels of Atalantia monophylla. All compounds were tested for cytotoxicity against HeLa, HCT116 and MCF-7 cell lines, as well as normal cells (Vero cells). Compound 5 showed cytotoxicity against HeLa, HCT116 and MCF-7 cell lines with IC₅₀ values ranging from 16-25?μg/mL but was inactive against Vero cells. Compound 6 also showed interesting results as compound 5 with IC₅₀ values ranging from 15-18?μg/mL and an IC₅₀ value of 80.20?μg/mL against Vero cells. This means compounds 5 and 6 can be used as lead compounds for anticancer agents.     

Isolation and structural modifications of ananixanthone from Calophyllum teysmannii and their cytotoxic activities

Two naturally occurring xanthones, ananixanthone (1) and β-mangostin (2), were isolated using column chromatographic method from the n-hexane and methanol extracts of Calophyllum teysmannii, respectively. The major constituent, ananixanthone (1), was subjected to structural modifications via acetylation, methylation and benzylation yielding four new xanthone derivatives, ananixanthone monoacetate (3), ananixanthone diacetate (4), 5-methoxyananixanthone (5) and 5-O-benzylananixanthone (6). Compound 1 together with its four new derivatives were subjected to MTT assay against three cancer cell lines; SNU-1, K562 and LS174T. The results indicated that the parent compound has greater cytotoxicity capabilities against SNU-1 and K562 cell lines with IC₅₀ values of 8.97 ± 0.11 and 2.96 ± 0.06 μg/mL, respectively. Compound 5 on the other hand exhibited better cytotoxicity against LS174T cell line with an IC₅₀ value of 5.76 ± 1.07 μg/mL.     

In vitro and in silico study of Aloe vera leaf extract against human breast cancer

Abstract

Aloe vera leaf contains some bioactive compounds that have a strong binding affinity toward estrogen receptor as compared to standard drug tamoxifen. In this study, we have found that the IC₅₀ of Aloe vera leaf extract against breast cancer cell line (MCF-7) is 23?µg/mL which is much lower than the IC₅₀ (332?µg/mL) of Aloe vera leaf extract against non-cancerous cell line (NIH-3T3). We have also calculated the total concentration of phenolic acid (385.662?µg/mL), flavonoids (160.402?µg/mL) and alkaloids (276.754?µg/mL) in Aloe vera leaf extract. The free radical scavenging activity of Aloe vera leaf extract is 67% to 89% (at 50 to 300?µg/ml). Our virtual molecular docking study suggests that bioactive compounds like Aloe-emodin (?8.8?Kcal/mol), 7-hydroxy-2,5 dimethylchromone (?7.5?Kcal/mol), Beta-sitosterol (?7.3?Kcal/mol) etc. have a greater binding affinity toward estrogen alpha receptor as compared to standard drug Tamoxifen (?6.4?Kcal/mol).

     

The new ether derivative of phenylpropanoid and bioactivity was investigated from the leaves of Piper betle L.

Abstract

A new ether derivative of phenylpropanoid compound, γ-(γ′-isohydroxychavicol)-chavicol octanyl ether (K1) along with one known phenylpropanoid named allyl-pyrocatechol or hydroxychavicol (2) were isolated from Piper betle var. kali collected from Tumluk district, West Bengal India. We first report the presence of compound K1 in the genus Piper. Their structures were established on the basis of various spectroscopic analyses. Compounds K1 and 2 showed excellent antioxidant DPPH free radical scavenging activity with IC₅₀ values of 4.61 and 4.12?µg/mL compared to ascorbic acid as a standard antioxidant drug with IC₅₀ value of 3.42?µg/mL, respectively. Evaluation of in vitro cytotoxic activities of compounds K1 and 2 showed significant effects against human oral cancer cell lines (AW13516 and AW8507), human hepatoma cell lines (HEPG2 and PLC-PRF-5) and a human pancreatic cell line (MIA-PA-CA-2), compared to Doxorubicin^® as a standard cytotoxic drug with GI₅₀ values of <10 and 18.18?µg/mL.     

HPLC-DAD-SPE-NMR isolation of tetracyclic spiro-alkaloids with antiplasmodial activity from the seeds of Erythrina latissima

Abstract

Seven tetracyclic spiro-alkaloids, i.e. glucoerysodine (1), erysodine (2), epi-erythratidine (3), erysovine (4), erythratidine (5), erysotrine (6) and erythraline (7) were isolated from the seeds of Erythrina latissima by means of conventional separation methods and HPLC-DAD-SPE-NMR. Their structures were elucidated by spectroscopic means. This is the first report on the isolation of compounds 3, 5 and 6 from this plant. Antiplasmodial activity against the chloroquine-resistant strain Plasmodium falciparum K1 and cytotoxicity against MRC-5 cells (human fetal lung fibroblast cells) was assessed in vitro. Erysodine (2) and erysovine (4) showed moderate activity (IC₅₀ 6.53?µM and 4.05?µM, respectively), compared with the standard chloroquine (IC₅₀ = 0.14?µM). No cytotoxicity was observed in a concentration up to 64.0?µM.     

Blennolide derivatives from the soil-derived fungus Trichoderma asperellum PSU-PSF14

Three new blennolide derivatives, blennolides L-N (1–3), together with five known metabolites were isolated from the soil-derived fungus Trichoderma asperellum PSU-PSF14. Their structures were determined by analysis of spectroscopic data. Their relative configurations were determined by analysis of NOEDIFF data and confirmed by X-ray crystallography for compound 1 whereas the absolute configurations were established by means of experimental and calculated TDDFT ECD data. Compound 1 displayed antifungal activity against Cryptococcus neoformans ATCC90112 and ATCC90113 flucytosine-resistant with the MIC values of 128 and 64?μg/mL, respectively, and was inactive against noncancerous Vero cell lines.     

Antiplasmodial prenylated flavanonols from Tephrosia subtriflora

The CH₂Cl₂/MeOH (1:1) extract of the aerial parts of Tephrosia subtriflora afforded a new flavanonol, named subtriflavanonol (1), along with the known flavanone spinoflavanone B, and the known flavanonols MS-II (2) and mundulinol. The structures were elucidated by the use of NMR spectroscopy and mass spectrometry. The absolute configuration of the flavanonols was determined based on quantum chemical ECD calculations. In the antiplasmodial assay, compound 2 showed the highest activity against chloroquine-sensitive Plasmodium falciparum reference clones (D6 and 3D7), artemisinin-sensitive isolate (F32-TEM) as well as field isolate (KSM 009) with IC₅₀ values 1.4–4.6 μM without significant cytotoxicity against Vero and HEp2 cell lines (IC₅₀ > 100 μM). The new compound (1) showed weak antiplasmodial activity, IC₅₀ 12.5–24.2 μM, but also showed selective anticancer activity against HEp2 cell line (CC₅₀ 16.9 μM).     

Synthesis,crystal structures,and urease inhibition studies of two new Schiff-base copper complexes derived from n-butylamine

Two Schiff-base copper(II) complexes, bis(N-n-butyl-5-chlorosalicylaldiminato) copper(II) (1) and bis(N-n-butyl-4-methoxysalicylaldiminato) copper(II) (2), were synthesized and their solid-state structures were determined by X-ray crystallography. Complex 1 displays a distorted square-planar geometry, while 2 possesses square-planar geometry. Copper(II) complexes 1 and 2 showed strong inhibitory activity against jack bean urease (IC₅₀?=?2.7, 3.5?µmol?L^?1), compared with acetohydroxamic acid (IC₅₀?=?63.00?µmol?L^?1). A molecular modeling study was carried out via the DOCK program to gain understanding of the potent inhibitory activity of these copper species against jack bean urease.     

Antileishmanial diterpenoid alkaloids from Aconitum spicatum (Bruhl) Stapf

The crude extracts of tubers of Aconitum spicatum (Bruhl) Stapf were investigated for in vitro antileishmanial activity against Leishmania major. The dichloromethane extract at pH 2.5 showed antileishmanial activity with IC₅₀ value of 27.10 ± 0.0 μg/mL. Chromatographic purification of the dichloromethane extract led to isolation of three C-19 norditerpenoid alkaloids indaconitine (1), chasmaconitine (2) and ludaconitine (3). Compounds 3 and 2 showed antileishmanial activity with IC₅₀ = 36.10 ± 3.4 and 56.30 ± 2.1 μg/mL, respectively. Compound 1 was less effective (IC₅₀ > 100 μg/mL). The cytotoxicity of compounds 1, 2 and 3 studied against MCF7, HeLa and PC3 cancer cell lines and 3T3 normal fibroblast cell line did not show cytotoxicity at 30 μM.     

New 1, 2-naphthoquinone-derived pigments from the mycobiont of lichen Trypethelium eluteriae Sprengel

A new yellow pigment trypethelonamide A (1), and a new dark violet-red pigment 5′-hydroxytrypethelone (2), as well as three known dark violet-red pigments (+)-8-hydroxy-7-methoxytrypethelone (3), (+)-trypethelone (4) and (-)-trypethelone (5) were isolated from the cultured lichenized fungus Trypethelium eluteriae. The structures of 1 and 2 were determined to be 1, 2-naphthoquinone derivatives by extensive spectroscopic analysis. The absolute configurations of 1 and 2 were assigned by quantum electronic circular dichroism (ECD) calculation. All isolated compounds were evaluated for cytotoxicities against A549, HepG2 and RKO cell lines, and antioxidant effects on DPPH. Compounds 1–5 showed moderate and weak cytotoxicities against RKO cell line with IC₅₀ from 22.6 to 113.5 μM.     

Bioactive xanthoquinodins and epipolythiodioxopiperazines from Chaetomium globosum 7s-1, an endophytic fungus isolated from Rhapis cochinchinensis (Lour.) Mart

Abstract

A new xanthoquinodin B9 (1), together with two known xanthoquinodins, xanthoquinodin A1 (2) and xanthoquinodin A3 (3), three epipolythiodioxopiperazines, chetomin (4), chaetocochin C (5) and dethio-tetra(methylthio)chetomin (6), and four other compounds, chrysophanol (7), emodin (8), alatinone (9), and ergosterol (10) were isolated from the endophytic fungus Chaetomium globosum 7s-1, isolated from Rhapis cochinchinensis (Lour.) Mart. All isolated structures were established based on their spectroscopic data analyses. Compounds 1–6 showed antibacterial activity against Gram positive bacteria with MICs ranging from 0.02?pM to 10.81 µM. Compounds 1–6 also exhibited cytotoxicity against KB, MCF-7 and NCI-H187 cancer cell lines (IC₅₀ 0.04–18.40 µM). However, they were cytotoxic towards a normal cell line (Vero cell) with IC₅₀ values ranging from 0.04 to 3.86 µM.     

Major terpenoids from Telekia speciosa flowers and their cytotoxic activity in vitro

In addition to known constituents of Telekia speciosa, an acetone extract from ray florets of the plant yielded: 5,5?-dibutoxy-2,2?-bifuran (1), 5,5?-diisobutoxy-2,2?-bifuran (2), α-tocopherol (3), β-tocopherol (4), loliolide palmitate (5), a mixture of calenduladiol esters - 16β-hydroxylupeol-3-O-palmitate (7) and 16β-hydroxylupeol-3-O-myristate (8), 1-epiinuviscolide (12), inuviscolide (13), 3-epiisotelekin (16), 4α-hydroxy-9β,10β-epoxy-1β(H)-11(13)-guaien-8α,12-olide (17), 4α-hydroxy-1β(H)-9(10),11(13)-guaiadien-8α,12-olide (18), loliolide (19) and 4β,10β-dihydroxy-1α(H),5α(H)-11(13)-guaien-8α,12-olide (20). Calenduladiol esters and asperilin (14) were the major constituents of the extract. Their cytotoxic effect on human normal prostate epithelial cells (PNT-2), human prostate carcinoma cell lines, human skin fibroblasts (HSF) and human melanoma cell lines was examined in vitro. Triterpene esters showed no cytotoxicity against nearly all cell lines tested, except for Du145 prostate carcinoma cells (IC₅₀ – 62.0 μΜ). Asperilin displayed activity against the cell lines under study, especially against three tested lines of melanomas (A375, IC₅₀ – 17.6 μΜ, WM793, IC₅₀ – 28.2 μΜ and Hs 294T, IC₅₀ – 29.5 μΜ).