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).

     

A new furan derivative from an endophytic Aspergillus tubingensis of Decaisnea insignis (Griff.) Hook.f. & Thomson

A new furan derivative named 3-(5-oxo-2,5-dihydrofuran-3-yl) propanoic acid (1) was isolated for the first time. Its structure was elucidated by UV, IR, NMR, HR-ESI-MS and the single-crystal X-ray diffraction spectroscopic data. Meanwhile, the antifungal and antibacterial activities of compound 1 was tested, it exhibited potent antifungal activity against Fusarium graminearum with MIC value of 16?µg/mL and medium antibacterial activity against Streptococcus lactis with MIC value of 32?µg/mL.     

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.     

Antifungal activity of Mongolian medicinal plant extracts

Abstract

The in vitro antifungal activity of extracts obtained from 14 medicinal plants of the mongolian flora were investigated by measuring their minimal inhibitory concentration (MIC) against fungi cause of cutaneous diseases such as Candida species, dermatophytes and Malassezia furfur. Among the species examined, Stellaria dichotoma L., Scutellaria scordifolia L. Aquilegia sibirica Fisch. Et Schrenk. and Hyoscyamus niger L. extracts demonstrated antifungal activity against all studied fungi. In particular, S. scordifolia L. methanol extract, obtained at room temperature, showed the best activity against Candida spp., Malassezia furfur and dermatophytes with GMMIC₅₀ values of 22?µg/mL, 64?µg/mL and 32?µg/mL, respectively. The flavones, luteolin and apigenin, identified in S. scordifolia extracts, and rutin identified in S. dichotoma and Hyoscyamus niger L. extracts, could be responsible of the observed antifungal activity.     

Synthesis of spirooxindoles promoted by the deep eutectic solvent,ZnCl2+urea via the pseudo four-component reaction: anticancer,antioxidant, and molecular docking studies

Abstract

Various spirooxindoles (7a–c, 8a–c, 9a–c, and 10a–c) were efficiently synthesized using deep eutectic solvent ZnCl₂+urea and well characterized using IR, ¹H NMR, and ¹³C NMR spectroscopic techniques. The biological screening results showed that the compound 9a exhibited potent anticancer activity against MCF7 and HeLa cell lines with IC₅₀ values 6.47?±?0.01 and 9.14?±?0.32?µM, respectively. The compound 7c exhibited potent activity against the HeLa cell line with IC₅₀ value 6.81?±?0.01?µM. The compound 9a exhibited a potent antioxidant activity with IC₅₀ value 7.34?±?0.17?µM. The comparative molecular docking study against the cancer proteins EGFR and HER2 revealed that the EGFR was the best target protein receptor for the target compounds. Among all the compounds, the compound 9a exhibited the least binding energy ?10.72?kcal/mol against the protein EGFR (PDB ID: 4HJO).     

Synthesis of new bicarbazole-linked triazoles as non-cytotoxic reactive oxygen species (ROS) inhibitors

Abstract

Carbazole analogs 3 and 4 and a new library of bicarbazole-linked triazoles 6–11 were prepared via new synthetic methodology. Metal-catalyzed oxidative coupling reaction was utilized for the synthesis of bicarbazole acetylene 4 and different metals (Zn⁺², Co⁺², Fe⁺³, Ni⁺², Cu⁺², Mn⁺²) as catalyst were screened. Only Fe-catalyzed reaction was found to be excellent and gave homocoupled product 4. Cu-catalyzed 1,3-dipolar cycloaddition was also utilized to install triazole moiety for the synthesis of hybrid molecules 6–11. Based on reported anti-inflammatory activity of carbazole and triazole scaffolds, all compounds were screened for their reactive oxygen species (ROS) inhibitory potential. Results from these studies revealed triazole 9 as most active compound (IC₅₀ value of 7.6?±?0.1?µg/mL on human whole blood and 2.7?±?0.09?µg/mL on isolated neutrophils) using ibuprofen as a standard. Therefore, class described herein can serve as attractive structural element for further studies on ROS inhibition.     

Efficient and convenient synthesis,characterization, and antimicrobial evaluation of some new tetracyclic 1,4-benzothiazines

In the present study, 20 new tetracyclic 1,4-benzothiazines (4a–4 t) were conveniently synthesized in good yields and characterized by different spectral and physical techniques. The in vitro antimicrobial evaluation of the synthesized benzothiazine derivatives was performed by serial dilution against two Gram-positive bacteria [Bacillus subtilis (MTCC 441) and Staphylococcus epidermidis (MTCC 6880)], two Gram-negative bacteria [Escherichia coli (MTCC 1652) and Pseudomonas aeruginosa (MTCC 424)], and two fungal strains [Candida albicans (MTCC 227) and Aspergillus niger (MTCC 8189)]. The derivatives 4 l and 4 t were found to be more potent than standard drug, i.e., fluconazole, against A. niger and C. albicans, respectively.     

Stereoselective synthesis of the lichen metabolite, (+) montagnetol and its congeners as antimicrobial agents

Abstract

In view of structural diversity, (+) montagnetol, the major metabolite of the fruticose lichen, Roccella montagnei was synthesized along with three of its congeners by employing highly efficient protocols. (+) Montagnetol (2?R, 3S; 11) and (-) montagnetol (2S, 3R; 5) were synthesized in 7 and 9 steps, respectively, from L-ascorbic acid. The two new congeners 3 (2?R, 3R) and 6 (2S, 3S), which differ in configuration at C-2 and C-3 positions of the (+) montagnetol, were synthesized from (?) diethyl D-tartrate and (+) diethyl L-tartrate, respectively. The synthesized compounds were evaluated in vitro for antimicrobial activity against two Gram-positive (S. aureus and E. coli) and two Gram-negative (S. typhi and P. aeruginosa) bacteria and one fungal strain Candida albicans. Interestingly, the congener 3 showed promising anti-bacterial activity (MIC: 0.062?µg/ml) against P. aeruginosa, whereas the congener 6 displayed potent anti-fungal activity (MIC: 0.062?µg/ml) against C. Albicans.     

Chemical constituents and cytotoxic activity from the wood-decaying fungus Xylaria sp. SWUF08-37

Abstract

A new cyclic pentapeptide, pentaminolarin (1), and a new cytochalasin, xylochalasin (2), along with thirteen known compounds (3–15) were isolated from the wood-decaying fungus Xylaria sp. SWUF08-37. The absolute configurations of 1 were determined by a combination of Marfey’s method and TDDFT ECD calculation and the absolute configurations of 2 were established by TDDFT ECD calculation. Compound 12 showed moderate cytotoxicity against HeLa (IC₅₀?=?19.60?µg/mL), HT29 (IC₅₀?=?17.31?µg/mL), HCT116 (IC₅₀?=?14.28?µg/mL), MCF-7 (IC₅₀?=?15.38?µg/mL), and Vero (IC₅₀?=?24.97?µg/mL) cell lines by MTT assay. Compounds 1 and 2 showed slight cytotoxicity against all tested cancer cell lines.     

黄烷类衍生物的合成及其生物活性研究

An efficient and feasible synthetic approach was developed for the synthesis of an array of new flavane derivafives from the substituted benzaldehyde with the reduction of chalcones and subsequent cyclization as the key steps. The purity and structure of the products were confirmed by the elemental analysis and a combination of its IR, ^1H and ^13C NMR, and mass spectra. These synthetic compounds were tested for xanthine oxidase （XO） inhibitions and antifungal actions against Candida albicans, Cryptococcus neoformans, Aspergillus sp. and Trichophyton rubrum. 7-Hydrazinocarbonylmethoxy-4＇-methoxyflavane （9） was found to be the most XO inhibitory with IC50=76.4 μmol/L, and the most potent antifungal compound was 4＇-hydrazinocarbonylmethoxyflavane （12） with minimal inhibition concentration MIC=8 μg/mL against Trichophyton rubrum.     

Inula viscosa (L.) Aiton leaves and flower buds: Effect of extraction solvent/technique on their antioxidant ability,antimicrobial properties and phenolic profile

Abstract

This study was designed to establish the most effective solvent/technique for extracting antioxidant phytoconstituents from leaves and flower buds of Inula viscosa (L.) Aiton (Asteraceae) grown wild in Morocco. Maceration and hot extraction with methanol or water and Soxhlet ethanol extraction were utilized. The antioxidant potential was evaluated in vitro by DPPH, reducing power, and ferrous ions chelating activity assays. I. viscosa leaf and flower bud extracts displayed the strongest effect in the DPPH test, being the Soxhlet ethanol the most active ones (IC₅₀ = 54.24?±?0.21?μg/mL and 39.77?±?0.23?μg/mL); thus, they were selected for further investigations. The antimicrobial efficacy of the Soxhlet ethanol extracts against ATCC and food isolates strains was assayed; the leaf extract showed the best activity, and Candida albicans was the most sensitive strain (MIC = 125?µg/mL). The extracts resulted non-toxic against Artemia salina. Among the phenolics characterised by HPLC-PDA-ESI-MS, hispidulin hexoside, patuletin and spinacetin were identified for the first time.     

Antimicrobial secondary metabolites of an endolichenic Aspergillus niger isolated from lichen thallus of Parmotrema ravum

Abstract

A new 6-benzyl-γ-pyrone (1), named aspergyllone was isolated from the culture filtrates of an endolichenic fungus Aspergillus niger Tiegh, obtained from lichen thallus Parmotrema ravum (Krog & Swinscow) Serus, collected in India. 1 was isolated for the first time from an endolichenic fungus together with six other known metabolites identified as aurasperones A (2) and D (3), asperpyrone A (4), fonsecinone A (5), carbonarone A (6) and pyrophen (7). The compounds were tested against a panel of human, plant, food borne and fish pathogens. Aspergyllone showed strong selective antifungal activity against Candida parapsilosis (Ashford) Langeron & Talice, with an IC₅₀ of 52?µg/mL. Aurasperone A and pyrophen showed moderate to strong antimicrobial activity inhibiting seven different test pathogens, being pyrophen active with IC₅₀ ranging from 35 to 97?µg/mL.

     

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.     

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.     

Different Heterocycles Functionalized s‐Triazine Analogues: Design,Synthesis and In Vitro Antimicrobial,Antituberculosis, and Anti‐HIV Assessment

Some new quinolone condensed s‐triazine derivatives endowed with different heterocycles and 4‐aminobenzonitrile moiety has been synthesized and examined for their bioactivities against eight bacteria (Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, and Shigella flexneri), two fungi (Aspergillus niger, Candida albicans) by using agar streak dilution method, and Mycobacterium tuberculosis H37Rv by using Lowenstein and Jensen MIC method. Upon preliminary biological screening, it was observed that the majority of the compounds were found to possess a significant broad spectrum antimicrobial (MICs: 6.25–25 µg/mL) and antitubercular (MIC: 12.5 µg/mL) potential. Hence, anti‐HIV activity against two types of HIV viral strains [HIV‐1 (III_B) and HIV‐2 (ROD)] has been carried out using the MTT assay. From this bioassay, we have identified some potent inhibitors acting as anti‐HIV‐1 agents (IC₅₀: 4.45 µg/mL) with promising therapeutic index of 16 for analogue 7 h. The structural assignments of the new products were carried out on the basis of IR, ¹H NMR, ¹³C NMR spectroscopy, and elemental analysis.     

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.     

Monooxovanadium(V) 2-phenylphenoxides: synthesis,characterization, and antimicrobial potential

Monooxovanadium(V) complexes of the composition VOCl_{3? n} (L) _n (where L = 2-phenylphenoxide ion; n = 1–3) (1–3) have been synthesized in quantitative yields by the reaction of VOCl₃ with 2-phenylphenol in toluene. The characterization of the complexes has been accomplished by elemental analysis, molar conductance measurements, IR, ¹H-NMR, electronic, mass spectral, and thermal studies. The ligands as well as the complexes have been screened for their in vitro antimicrobial activity against the pathogenic bacteria Escherichia coli and Staphylococcus aureus and fungi Candida albicans, Aspergillus niger, and Fusarium oxysporum by a twofold serial dilution. An increase in the biocidal activity was observed for the vanadium complexes. The minimum inhibitory concentration (MIC) values were 6.25–25 µg mL^?1 for complexes, relative to that of the free ligand of 25–50 µg mL^?1.     

Antibacterial and cytotoxic activities of phenolic constituents from the stem extracts of Spatholobus parviflorus

Abstract

A new 2-arylbenzofuran, spathobenzofuran (1), together with ten known compounds including a 2-arylbenzofuran, three pterocarpans and six isoflavones were isolated from the acetone crude extract of the stems of Spatholobus parviflorus. All compounds were characterised by spectroscopic methods. Compound 4 was active (MIC 8?µg/mL) against Gram-negative Pseudomonas aeruginosa TISTR 781 while compound 2 had modest activity against Gram-positive Staphylococcus aureus TISTR 1466 with a MIC value of 16?µg/mL. All isolated compounds showed no cytotoxicity against Vero and KB cells.     

Synthesis and Biological Activity of Novel Furan/Thiophene and Piperazine‐Containing (Bis)1,2,4‐triazole Mannich Bases

Series of novel furan/thiophene and piperazine‐containing 1,2,4‐triazole Mannich bases and bis(1,2,4‐triazole) Mannich bases have been conveniently synthesized via Mannich reaction with triazole Schiff bases, various piperazine derivatives, and formaldehyde as intermediates in good yields. Their structures were characterized by melting points, ¹H NMR, ¹³C NMR, IR and elemental analysis. The preliminary bioassay showed that most compounds exhibited significant in vitro and in vivo fungicidal activity against several test plant fungi. Among 32 new compounds, the trifluoromethyl‐containing compounds showed superior activity than the methyl‐containing ones. Several compounds, such as F8 , F9 , F10 , G5 , H7 , H8 , I3 and I4 , were comparable with some commercial fungicides against different fungi during the present study and could be further structurally optimized. Meanwhile, several compounds showed good herbicidal activity against Brassica campestris at 100 µg/mL and KARI inhibitory activity at 200 µg/mL. However, compounds exhibited poor insecticidal activity against oriental armyworm at 200 µg/mL in the preliminary studies. The research results will provide useful information for the design and discovery of new agrochemicals with novel heterocyclic structures.     

Insecticidal,cytotoxic and anti-phytopathogenic fungal activities of chemical constituents from the aerial parts of Ferula sinkiangensis

Abstract

A new rare monoterpene coumarin (1) and its two known analogues (2–3), together with two sesquiterpenes (6–7) and ferulic acid (8) were isolated from the aerial parts of Ferula sinkiangensis. The structure of new compound was established on the basis of 1D and 2D NMR data and HRESIMS data interpretation. Insecticidal, cytotoxic and anti-phytopathogenic fungal activities of isolated compounds were evaluated against third-instar larvae of Spodoptera exigua and its cell line, and three plant pathogenic fungi respectively. Compounds 1–3 and 6–7 were found to be more effective contact toxicity to S. exigua with the corrected mortality values of 38.89%-58.89% at 10?μg/larva doses for 24?h. Further studies showed that compounds 3 and 6 exhibited cell growth inhibitory activity against S. exigua cell line with the EC₅₀ values of 22.78 and 14.64?µM for 72?h. In addition, compound 6 exhibited potent antifungal activity with MICs?=?16–32?µg/mL.