A series of novel 3-hydroxy-3-(2-imino-3-methyl-5-oxoimidazolidin-4-yl)indolin-2-one analogs (3) have been synthesized under microwave irradiation and conventional heating methods. These analogs were ...evaluated for their in vitro cytotoxicity against a panel of 57 human tumor cell lines. Compound 3o had GI50 values of 190nM and 750nM against A549/ATTC non-small cell lung cancer and LOX IMVI melanoma cell lines, respectively, and both 3n and 3o exhibited GI50 values ranging from 2 to 5μM against CCRF-CEM, HL-60(TB), K-562, MOLT-4, and RPMI-8226 leukemia cell lines. These results indicate that N-4-methoxybenzyl-3-hydroxy-(2-imino-3-methyl-5-oxo-4-yl)indolin-2-one analogs may be useful leads for anticancer drug development.
A series of novel 3-hydroxy-3-(2-imino-3-methyl-5-oxoimidazolidin-4-yl)indolin-2-one analogs (3) have been synthesized under microwave irradiation and conventional heating methods. These analogs were evaluated for in vitro cytotoxicity against a panel of 57 human tumor cell lines. Compound 3o had GI50 values of 190nM and 750nM against A549/ATTC non-small cell lung cancer and LOX IMVI melanoma cell lines, respectively, and both 3n and 3o exhibited GI50 values ranging from 2 to 5μM against CCRF-CEM, HL-60(TB), K-562, MOLT-4, and RPMI-8226 leukemia cell lines. These results indicate that N-4-methoxybenzyl-3-hydroxy-(2-imino-3-methyl-5-oxo-4-yl)indolin-2-one analogs may be useful leads for anticancer drug development.
Chronic, low-grade inflammation has been implicated in aging and age-dependent conditions, including Alzheimer's disease, cardiomyopathy, and cancer. One of the age-associated processes underlying ...chronic inflammation is protein aggregation, which is implicated in neuroinflammation and a broad spectrum of neurodegenerative diseases such as Alzheimer's, Huntington's, and Parkinson's diseases. We screened a panel of bioactive thiadiazolidinones (TDZDs) from our in-house library for rescue of protein aggregation in human-cell and
models of neurodegeneration. Among the tested TDZD analogs, PNR886 and PNR962 were most effective, significantly reducing both the number and intensity of Alzheimer-like tau and amyloid aggregates in human cell-culture models of pathogenic aggregation. A
strain expressing human Aβ
in muscle, leading to AD-like amyloidopathy, developed fewer and smaller aggregates after PNR886 or PNR962 treatment. Moreover, age-progressive paralysis was reduced 90% by PNR886 and 75% by PNR962, and "healthspan" (the median duration of spontaneous motility) was extended 29% and 62%, respectively. These TDZD analogs also extended wild-type
lifespan by 15-30% (
< 0.001), placing them among the most effective life-extension drugs. Because the lead drug in this family, TDZD-8, inhibits GSK3β, we used molecular-dynamic tools to assess whether these analogs may also target GSK3β. In silico modeling predicted that PNR886 or PNR962 would bind to the same allosteric pocket of inactive GSK3β as TDZD-8, employing the same pharmacophore but attaching with greater avidity. PNR886 and PNR962 are thus compelling candidate drugs for treatment of tau- and amyloid-associated neurodegenerative diseases such as AD, potentially also reducing all-cause mortality.
In recent years, Indian Ophioglossum L. taxonomy and systematic are receiving increasing interest from pteridologists as India has very rich germplasm of the genus. We present hereunder a new species ...of the genus Ophioglossum (Ophioglossaceae) from the marshy areas of southern region of Gujarat state, India. Ophioglossum hitkishorei sp. nov. can be diagnosed from other congeners by a combination of its smaller size, globose to subglobose, non-stoloniferous rhizome, number of trophophylls up to six, the absence of persistent leaf bases at top of rhizome and by very unique structure of spores. Spores are typically characterized by possessing granules deposition as exine strings bound around spores on the distal face and granulate assemblage on the proximal face of triradiate spores observed under SEM and also clearly distinct under light microscopic observations. As far as known, beaded strings of exine ornamentation have never been observed in any species of Ophioglossum in the world flora. Molecular study, based on two chloroplast DNA sequences trnL-F and psbA-trnH, also strongly supports O. hitkishorei sp. nov. as a distinct new species.
A series of novel substituted (
Z)-5-((1-benzyl-1
H-indol-3-yl)methylene) imidazolidin-2,4-diones (
3a–
f) and (
Z)-5-((1-benzyl-1
H-indol-3-yl)methylene)-2-iminothiazolidin-4-ones (
3g–
o) have been ...synthesized and evaluated for in vitro cytotoxicity against a panel of 60 human tumor cell lines
. Compound
3i exhibits potent growth inhibition against melanoma UACC-257 (GI
50
=
13.3
nM) and ovarian OVCAR-8 (GI
50
=
19.5
nM) cancer cells and significant cytotoxicity (LC
50
=
308 and 851
nM, respectively) against the same cell lines within this series of compounds. A second analog,
3a, had GI
50 values of 307 and 557
nM against SK-MEL-2 melanoma and A498 renal cancer cell lines, and exhibited GI
50 values ranging from 0.30 to 6
μM against 98% of the cancer cell lines in the 60-cell panel.
A series of novel substituted (
Z)-5-((1-benzyl-1
H-indol-3-yl)methylene)imidazolidin-2,4-diones (
3a–
f) and (
Z)-5-((1-benzyl-1
H-indol-3-yl)methylene)-2-iminothiazolidin-4-ones (
3g–
o) have been synthesized utilizing microwave irradiation. These analogs were evaluated for in vitro cytotoxicity against a panel of 60 human tumor cell lines
. Compound
3i exhibits potent growth inhibition against melanoma UACC-257 (GI
50
=
13.3
nM) and OVCAR-8 ovarian (GI
50
=
19.5
nM) cancer cells while possessing significant cytotoxicity (LC
50
=
308
nM and LC
50
=
851
nM, respectively) against the same cell lines within this series of compounds. A second analog,
3a, had GI
50 values of 307 and 557
nM against SK-MEL-2 melanoma and A498 renal cancer cell lines, and exhibited GI
50 values ranging from 0.30 to 6
μM against 98% of all cancer cell lines in the 60-cell panel. Thus, (
Z)-5-((5-chloro-1-(4-fluorobenzyl)-1
H-indol-3-yl)methylene)-2-iminothiazolidin-4-one (
3i) and (
Z)-methyl 1-(4-cyanobenzyl)-3-((2,5-dioxoimidazolidin-4-ylidene)methyl)-1
H-indole-6-carboxylate (
3a) can be regarded as useful lead compounds for further structural optimization as antitumor agents.
In the present study, highest hydrogen production by
Rhodobacter sphaeroides
was seen in lactose and mannitol as carbon sources. Glutamic acid and tyrosine induced the highest production of hydrogen. ...Cyanocobalamine induced the highest production of hydrogen. Enhancement of hydrogen production by 23% was seen after knocking out of the hydrogen reuptake hydrogenase gene. Large-scale production of hydrogen can be tried with this genetically engineered organism, provided some safety aspects are taken into consideration, especially with storage as hydrogen explodes when it comes in contact with air.
Background
The objective of the study is to evaluate the hepatoprotective activity of methanolic extract fractions of
Lindernia ciliata
(LC) and development of qualitative analytical profile of the ...bioactive fraction using HPLC fingerprinting analysis. All the fractions of methanolic extract of
Lindernia ciliata
(LCME) are assessed for their total phenolic, flavonoid contents and in vitro antioxidant properties by using DPPH, superoxide, nitric oxide, hydroxyl radical scavenging activities and reducing power assay. Acute toxicity study was conducted for all the fractions and the two test doses 50 and 100 mg/kg were selected for the hepatoprotective study. Liver damage was induced in different groups of rats by administering 3 g/kg.b.w.p.o. paracetamol and the effect of fractions were tested for hepatoprotective potential by evaluating serum biochemical parameters and histology of liver of rats. The effective fraction was evaluated for its antihepatotoxic activity against D-Galactosamine (400 mg/kg b.w. i.p.) and in vivo antioxidant parameters viz., Glutathione (GSH), Melondialdehyde (MDA) and Catalase (CAT) levels are estimated using liver homogenate.
Results
Among all the fractions, butanone fraction of LCME, (BNF-LCME) has shown better hepatoprotective activity and hence it is selected to evaluate the antihepatotoxicity against D-GaIN. The activity of BNF-LCME is well supported in in vitro and in vivo antioxidant studies and may be attributed to flavonoidal, phenolic compounds present in the fraction. Hence, BNF-LCME was subjected to the development of qualitative analytical profile using HPLC finger printing analysis.
Conclusions
All the fractions of LCME exhibited significant hepatoprotective activity and BNF-LCME (50 mg/kg) was identified as the most effective fraction.
The rhizomes of Alpinia galanga (L.) Willd (Zingiberaceae), a ginger substitute for flavouring food was traditionally used as nervine tonic and stimulant.
This investigation is designed to screen ...cognitive improvement of Alpinia galanga (AG) fractions in Alzheimer's type of amnesia in mice induced by Aβ(25–35).
Alzheimer's disease induced mice treated with fractions (n-hexane, chloroform and ethyl acetate) of AG in 200 and 400mg/kg. Neurotoxicity was induced by intracerebroventricular injection of Aβ(25–35) on the 14th day of 21 days drug treatment. Open field and water maze were carried to determine habituation memory and hippocampal memory. Na+/K+-ATPase, acetylcholinesterase (AChE) and antioxidant enzymes (SOD, GPx, catalase and vitamin C) were determined in brain tissue homogenate to estimate the brain biochemical changes and its anti-amnesic potential with intensity of oxidative stress signaling. Further bioactive (chloroform) fraction was eluted through column chromatography to identify the lead molecules.
Increased habituation memory and decreased escape latency in behavioral parameter are the indicative of the cognitive enhancement after treatment with Alpinia galanga fractions. Increment in Na+/K+-ATPase and antioxidant activity depicts brain membrane integrity improvement and free radical scavenging property. AChE level was decreased to improve the cognition by enhancing cholinergic transmission.
Anti-amnesic effect was exerted by various fractions of Alpinia galanga. Among all fractions, preeminent neuroprotection was exerted by chloroform fraction, which has compound, 1′δ-1′-acetoxyeugenol acetate and it may be a potential therapeutic agent for Alzheimer's type of amnesia. These results further motivate us to explore the activity of lead compound's anti-amnesic effect on transgenic mice model of AD.
The 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) oxidation of cellulose, when mediated with Oxone
(KHSO
), can be performed simply and under mild conditions. Furthermore, the products of the reaction ...can be isolated into two major components: Oxone
-mediated TEMPO-oxidized cellulose nanomaterials Form I and Form II (OTO-CNM Form I and Form II). This study focuses on the characterization of the properties of OTO-CNMs. Nanoparticle-sized cellulose fibers of 5 and 16 nm, respectively, were confirmed through electron microscopy. Infrared spectroscopy showed that the most carboxylation presented in Form II. Conductometric titration showed a two-fold increase in carboxylation from Form I (800 mmol/kg) to Form II (1600 mmol/kg). OTO-CNMs showed cellulose crystallinity in the range of 64-68% and crystallite sizes of 1.4-3.3 nm, as shown through XRD. OTO-CNMs show controlled variability in hydrophilicity with contact angles ranging from 16 to 32°, within or below the 26-47° reported in the literature for TEMPO-oxidized CNMs. Newly discovered OTO-CNM Form II shows enhanced hydrophilic properties as well as unique crystallinity and chemical functionalization in the field of bio-sourced material and nanocomposites.
Ilimaquinone (IQ), a metabolite found in marine sponges, has been reported to have a number of biological properties, including potential anticancer activity against colon cancer. However, no clear ...understanding of the precise mechanism involved is known. The aim of this study was to examine the molecular mechanism by which IQ acts on HCT-116 cells. The anticancer activity of IQ was investigated by means of a cell viability assay followed by the determination of induction of apoptosis by means of the use of acridine orange–ethidium bromide (AO/EB) staining, Annexin V/PI double staining, DNA fragmentation assays, and TUNEL assays. The mitochondrial membrane potential (ΔΨm) was detected using the JC-1 staining technique, and the apoptosis-associated proteins were analyzed using real-time qRT-PCR. A molecular docking study of IQ with apoptosis-associated proteins was also conducted in order to assess the interaction between IQ and them. Our results suggest that IQ significantly suppressed the viability of HCT-116 cells in a dose-dependent manner. Fluorescent microscopy, flow cytometry, DNA fragmentation and the TUNEL assay in treated cells demonstrated apoptotic death mode. As an additional confirmation of apoptosis, the increased level of caspase-3 and caspase-9 expression and the downregulation of Bcl-2 and mitochondrial dysfunction were observed in HCT-116 cells after treatment with IQ, which was accompanied by a decrease in mitochondrial membrane potential (ΔΨm). Overall, the results of our studies demonstrate that IQ could trigger mitochondria-mediated apoptosis as demonstrated by a decrease in ΔΨm, activation of caspase-9/-3, damage of DNA and a decrease in the proportion of Bcl-2 through the mitochondrial-mediated apoptosis pathway.
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