Several compounds isolated from Dryobalanops have been reported to exhibit cytotoxic effects to several cancer cell lines. This study investigated the cytotoxic effects, cell cycle arrest and mode of cell death in ampelopsin E-treated triple negative cells, MDA-MB-231.
A library of novel 2,5-disubtituted-1,3,4-oxadiazoles with benzimidazole backbone (3a-3r) was synthesized and evaluated for their potential as β-glucuronidase inhibitors. Several compounds such as 3a-3d, 3e-3j, 3l-3o, 3q and 3r showed excellent inhibitory potentials much better than the standard (IC50=48.4±1.25μM: d-saccharic acid 1,4-lactone). All the synthesized compounds were characterized satisfactorily by using different spectroscopic methods. We further evaluated the interaction of the active compounds and the enzyme active site with the help of docking studies.
Bisindolylmethane thiosemicarbazides 1-18 were synthesized, characterized by 1H NMR and ESI MS and evaluated for urease inhibitory potential. All analogs showed outstanding urease inhibitory potentials with IC50 values ranging between 0.14 ± 0.01 to 18.50 ± 0.90 μM when compared with the standard inhibitor thiourea having IC50 value 21.25 ± 0.90 μM. Among the series, analog 9 (0.14 ± 0.01 μM) with di-chloro substitution on phenyl ring was identified as the most potent inhibitor of urease. The structure activity relationship has been also established on the basis of binding interactions of the active analogs. These binding interactions were identified by molecular docking studies.
Apoptotic cell death is the cause of the loss of insulin-producing β-cells in all forms of diabetes mellitus. The identification of small molecules capable of protecting cytokine-induced apoptosis could form the basis of useful therapeutic interventions. Here in, we present the discovery and synthesis of new benzimidazole derivatives, capable of rescuing pancreatic β-cells from cytokine-induced apoptosis. Three hydrazone derivatives of benzimidazole significantly increased the cellular ATP levels, reduced caspase-3 activity, reduced nitrite production and increased glucose-stimulated insulin secretion in the presence of proinflammatory cytokines. These findings suggest that these compounds may protect β-cells from the harmful effects of cytokines and may serve as candidates for therapeutic intervention for diabetes.
Newly synthesized benzimidazole hydrazone derivatives 1-26 were evaluated for their α-glucosidase inhibitory activity. Compounds 1-26 exhibited varying degrees of yeast α-glucosidase inhibitory activity with IC50 values between 8.40 ± 0.76 and 179.71 ± 1.11 μM when compared with standard acarbose. In this assay, seven compounds that showed highest inhibitory effects than the rest of benzimidazole series were identified. All the synthesized compounds were characterized by different spectroscopic methods adequately. We further evaluated the interaction of the active compounds with enzyme with the help of docking studies.
Biscoumarin analogs 1-18 have been synthesized, characterized by EI-MS and (1)H NMR and evaluated for α-glucosidase inhibitory potential. All compounds showed variety of α-glucosidase inhibitory potential ranging in between 13.5±0.39 and 104.62±0.3μM when compared with standard acarbose having IC50 value 774.5±1.94μM. The binding interactions of the most active analogs were confirmed through molecular docking. The compounds showed very good interactions with enzyme. All synthesized compounds 1-18 are new. Our synthesized compounds can further be studied to developed lead compounds.
Novel series of disulfide and sulfone hybrid analogs (1-20) were synthesized and characterized through EI-MS and (1)H NMR and evaluated for β-glucuronidase inhibitory potential. All synthesized analogs except 13 and 15 showed excellent β-glucuronidase inhibitory potential with IC50 value ranging in between 2.20-88.16μM as compared to standard d-saccharic acid 1,4 lactone (48.4±1.25μM). Analogs 19, 16, 4, 1, 17, 6, 10, 3, 18, 2, 11, 14 and 5 showed many fold potent activity against β-glucuronidase inhibitor. Structure activity relationship showed that substitution of electron withdrawing groups at ortho as well as para position on phenyl ring increase potency. Electron withdrawing groups at meta position on phenyl ring showed slightly low potency as compared to ortho and para position. The binding interactions were confirmed through molecular docking studies.
In search of better α-glucosidase inhibitors, a series of bis-indolylmethane sulfonohydrazides derivatives (1-14) were synthesized and evaluated for their α-glucosidase inhibitory potential. All derivatives exhibited outstanding α-glucosidase inhibition with IC50 values ranging between 0.10 ± 0.05 to 5.1 ± 0.05 μM when compared with standard drug acarbose having IC50 value 856.28 ± 3.15 μM. Among the series, analog 7 (0.10 ± 0.05 μM) with tri-chloro substitution on phenyl ring was identified as the most potent inhibitor of α-glucosidase (∼ 8500 times). The structure activity relationship has been also established. Molecular docking studies were also performed to help understand the binding interaction of the most active analogs with receptors. From the docking studies, it was observed that all the active bis-indolylmethane sulfonohydrazides derivatives showed considerable binding interactions within the active site (acarbose inhibition site) of α-glucosidase. We also evaluated toxicity of all derivatives and found none of them are toxic.
Thiourea derivatives having benzimidazole 1-17 have been synthesized, characterized by 1H NMR, 13C NMR and EI-MS and evaluated for α-glucosidase inhibition. Identification of potential α-glucosidase inhibitors were done by in vitro screening of 17 thiourea bearing benzimidazole derivatives using Baker's yeast α-glucosidase enzyme. Compounds 1-17 exhibited a varying degree of α-glucosidase inhibitory activity with IC50 values between 35.83±0.66 and 297.99±1.20μM which are more better than the standard acarbose (IC50=774.5±1.94μM). Compound 10 and 14 showed significant inhibitory effects with IC50 value 50.57±0.81 and 35.83±0.66μM, respectively better than the rest of the series. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction of the compounds.
Due to the great biological importance of β-glucuronidase inhibitors, here in this study, we have synthesized a library of novel benzothiazole derivatives (1-30), characterized by different spectroscopic methods and evaluated for β-glucuronidase inhibitory potential. Among the series sixteen compounds i.e.1-6, 8, 9, 11, 14, 15, 20-23 and 26 showed outstanding inhibitory potential with IC50 value ranging in between 16.50 ± 0.26 and 59.45 ± 1.12 when compared with standard d-Saccharic acid 1,4-lactone (48.4 ± 1.25 µM). Except compound 8 and 23 all active analogs showed better potential than the standard. Structure activity relationship has been established.
The family Sterculiaceae is one of the most important families among flowering plants. Many of its members demonstrate medicinal properties and have been used for the treatment of various ailments and wounds. A wide range of compounds including alkaloids, phenyl propanoids, flavonoids, terpenoids and other types of compounds including hydrocarbons, sugars, quinones, phenolic acids, lactones, lignans, amine and amides have been isolated from several species in this family. Few studies have reported that some extracts and single compounds isolated from this family exhibited several biological activities, such as antimicrobial, anti-inflammatory, antioxidant and cytotoxic activities. The present review is an effort to provide information about the traditional uses, phytochemistry and pharmacology of species from family Sterculiaceae, and to uncover the gaps and potentials requiring further research opportunities regarding the chemistry and pharmacy of this family.
Thirty-two (32) bis-indolylmethane-hydrazone hybrids 1-32 were synthesized and characterized by 1HNMR, 13CNNMR and HREI-MS. All compounds were evaluated in vitro for β-glucuronidase inhibitory potential. All analogs showed varying degree of β-glucuronidase inhibitory potential ranging from 0.10 ± 0.01 to 48.50 ± 1.10 μM when compared with the standard drug d-saccharic acid-1,4-lactone (IC50 value 48.30 ± 1.20 μM). Derivatives 1-32 showed the highest β-glucuronidase inhibitory potentials which is many folds better than the standard drug d-saccharic acid-1,4-lactone. Further molecular docking study validated the experimental results. It was proposed that bis-indolylmethane may interact with some amino acid residues located within the active site of β-glucuronidase enzyme. This study has culminated in the identification of a new class of potent β-glucuronidase inhibitors.
The present study was conducted to determine the antinociceptive potential of methanol extract of Muntingia calabura L. (MEMC) and to isolate and identify the bioactive compound(s) responsible for the observed antinociceptive activity. The MEMC and its partitions (petroleum ether (PEP), ethyl acetate (EAP), and aqueous (AQP) partitions), in the dose range of 100, 500, and 1000 mg/kg, were tested using the formalin-induced nociceptive test. The PEP, which exerted the most effective activity in the respective early and late phase, was further subjected to the fractionation procedures and yielded seven fractions (labelled A to G). These fractions were tested, at the dose of 300 mg/kg, together with distilled water or 10% DMSO (negative controls); morphine and aspirin (positive controls) for potential antinociceptive activity. Of all fractions, Fraction D showed the most significant antinociceptive activity, which is considered as equieffective to morphine or aspirin in the early or late phase, respectively. Further isolation and identification processes on fraction D led to the identification of three known and one new compounds, namely, 5-hydroxy-3,7,8-trimethoxyflavone (1), 3,7-dimethoxy-5-hydroyflavone (2), 2',4'-dihydroxy-3'-methoxychalcone (3), and calaburone (4). At the dose of 50 mg/kg, compound 3 exhibited the highest percentage of antinociceptive activity in both phases of the formalin test. In conclusion, the antinociceptive activity of MEMC involved, partly, the synergistic activation of the flavonoid types of compounds.
A new oligostilbenoid tetramer, malaysianol B (1), was isolated from the acetone extract of the stem bark of Dryobalanops lanceolata along with seven oligostilbenoids tetramers; hopeaphenol (2), stenophyllol A (3), nepalensinol B (4), vaticanol B (5) and C (6), upunaphenol D (7), and flexuosol A (8). The structures of the isolated compounds were established on the basis of their spectroscopic data evidence. The antibacterial activity of the isolated compounds was evaluated using resazurin microtitre-plate assay.
A new flavanone derivative, malaysianone A (1), four prenylated flavanones, 6-prenyl-3'-methoxyeriodictyol (2), nymphaeol B (3), nymphaeol C (4) and 6-farnesyl-3',4',5,7-tetrahydroxyflavanone (5), and two coumarins, 5,7-dihydroxycoumarin (6) and scopoletin (7), were isolated from the dichloromethane extract of the inflorescences of Macaranga triloba. The structures of these compounds were elucidated based on spectroscopic methods including nuclear magnetic resonance (NMR-1D and 2D), UV, IR and mass spectrometry. The cytotoxic activity of the compounds was tested against several cell lines, with 5 inhibiting very strongly the growth of HeLa and HL-60 cells (IC(50): 1.3 μg/ml and 3.3 μg/ml, respectively). Compound 5 also showed strong antiplasmodial activity (IC(50): 0.06 μM).
A new resveratrol trimer, malaysianol A (1), five known resveratrol oligomers: laevifonol (2), ampelopsin E (3), α-viniferin (4), ε-viniferin (5), diptoindonesin A (6), and bergenin (7) have been isolated from the acetone extract of the stem bark of Dryobalanops aromatica by combination of vacuum and radial chromatography techniques. Their structures were established on the basis of their spectroscopic evidence and comparison with the published data. The cytotoxic activity of the compounds was tested against several cell lines in which compound 4 was found to inhibit strongly the growth of HL-60 cell line.
Hylocereus undatus foliage is believed to contain antioxidants similar to its peel. Numerous studies have been conducted to determine the total phenolic content (TPC) and antioxidant activity on the Hylocereus undatus pulps and peels; however, similar studies on its foliage have yet to be investigated. In this study, Hylocereus undatus foliage and peels were extracted using two different solvents namely; chloroform and methanol through Folin-Ciocalteu method and Diphenyl-1-Ipicrylhydrazyl (DPPH) free radical scavenging assay for TPC and antioxidant activity, respectively. As for TPC, results revealed that the peels gave higher TPC in both methanol (48.15 mg GAE/100g extract) and chloroform (18.89 mg GAE/100g extract) extractions than foliage (30.3 mg GAE/100g extract and 5.92 mg GAE/100g extract, respectively). However, when a comparison was made between foliage and peels in terms of its scavenging effects in DPPH assay, the peels contained more antioxidants (18.71%) than foliage (38.3%) in the chloroform solvent extracts. This study shows that Hylocereus undatus foliage has a similar antioxidant activity as its peels and is potentially a natural antioxidant in food applications.
A new tetramer oligostilbenoid possessing tetrahydrofuran ring, malaysianol C (1), was isolated from the acetone extract of the stem bark of Dryobalanops lanceolata, together with four known oligostilbenoids nepalensinol E (2), ϵ-viniferin (3), laevifonol (4), and ampelopsin F (5). The structures of isolated compounds were elucidated on the basis of spectral evidence. The antibacterial activity of the isolated compounds was evaluated using resazurin microtitre-plate assay, whereas the cytotoxic activity was tested using MTT assay. The plausible biogenetic routes of the isolated compounds are also discussed.
Several species from the genus Sapium possess a broad range of medicinal properties and they have been used as traditional medicines by indigenous groups in several regions such as Malaysia, Africa, Southern China and Bolivia. Most of the species reported to possess therapeutic effects which are used for the treatment of skin-related diseases such as eczema and dermatitis, but they may also be used for overstrain, lumbago, constipation and hernia. Species of this genus are also used to treat wounds and snake bites. In addition, the saps/latex of Sapium glandulosum, Sapium indicum and Sapium sebiferum have/has toxic effects and are used as bird and fish poisons. This review discusses the current knowledge of the medicinal uses, phytochemistry, biological activities and toxicities of species from the genus Sapium to reveal their therapeutic potentials and gaps offering opportunities for future research.
Pongamia pinnata (L.) Pierre is one of the many plants with diverse medicinal properties where all its parts have been used as traditional medicine in the treatment and prevention of several kinds of ailments in many countries such as for treatment of piles, skin diseases, and wounds.