Discovery of a marine-derived bis-indole alkaloid fascaplysin, as a new class of potent P-glycoprotein inducer and establishment of its structure-activity relationship.

The screening of IIIM natural products repository for P-gp modulatory activity in P-gp over-expressing human adenocarcinoma LS-180 cells led to the identification of 7 natural products viz. withaferin, podophyllotoxin, 3-demethylcolchicine, agnuside, reserpine, seseberecine and fascaplysin as P-gp inducers. Fascaplysin (6a), a marine-derived bis-indole alkaloid, was the most potent among all of them, showing induction of P-gp with EC50 value of 25 nM.

Inhibition of Invasion in Pancreatic Cancer Cells by Conjugate of EPA with β(3,3)-Pip-OH via PI3K/Akt/NF-kB Pathway.

The present work describes the anti-invasive effect of conjugate BC06, a novel conjugate of EPA, (2E,4E)-4-(benzo[d][1,3]dioxol-5-ylmethylene) hex-2-enoic acid with β,β-disubstituted-β-amino acid, β(3,3)-Pip-OH (2-(4-aminopiperidin-4-yl)acetic acid), in human pancreatic carcinoma. The conjugate BC06 inhibited invasion and migration of PANC-1 cells in wound healing, matrigel invasion, and gelatin degradation assays. Apart from suppressing PI3K/Akt/NF-kB signaling, which is involved in the up-regulation of matrix metalloproteinases, our study also demonstrated that dose-dependent treatment of BC06 results in the upregulation of TIMP-1 and E-cadherin expression.

Design, synthesis and anticancer activity of Michael-type thiol adducts of α-santonin analogue with exocyclic methylene.

A series of Michael-type analogues were generated on the C-ring of α-santonin (α-methylene-γ-butyrolactone) upon reaction with various thiols. All the thiol adducts synthesized were evaluated for their anticancer activity against four human cancer cell lines (PC-3, HCT-15, A-549 and MCF-7). Bioassay results indicated that even though most of the synthesized compounds exhibited a good anticancer activity against various cancer cells in vitro, some of the compounds like 9e, 9g and 9q were found to be the most promising analogues in this series, with compound 9e showing IC50 values of 1.

Development and evaluation of folate functionalized albumin nanoparticles for targeted delivery of gemcitabine.

Gemcitabine is one of the most potent anticancer agents acting on a wide range of solid tumors, however, its use is limited by short half life and high dose leading to serious side effects. The present investigation describes the development and characterization of folate functionalized gemcitabine loaded bovine serum albumin nanoparticles (Fa-Gem-BSANPs). The nanoparticles were prepared by desolvation cross-linking technique and characterized for various parameters including morphology, particle size, zeta potential, drug loading and release profile.

Synthesis, antimalarial and antitubercular activities of meridianin derivatives.

Meridianins are marine-derived indole alkaloids, known to possess kinase inhibitory and antimalarial activities. A series of N-aryl and heteroaryl sulfonamide derivatives of meridianins were prepared and screened for antimalarial activity against D6 and W2 strains of Plasmodium falciparum. 2-Nitro-4-trifluoromethyl sulfonamide derivative 14v displayed promising antiplasmodial activity against both strains with IC50 values of 2.

Anticancer activity and toxicity profiles of 2-benzylidene indanone lead molecule.

3-(3',4',5'-Trimethoxyphenyl)-4,5,6-trimethoxy,2-(3″,4″-methylenedioxybenzylidene)-indan-1-one (1) is an optimized anti-cancer lead molecule obtained on modification of gallic acid, a plant phenolic acid. It exhibited potent cytotoxicities (IC50=0.010-14.

Identification, cloning and characterization of an ultrapetala transcription factor CsULT1 from Crocus: a novel regulator of apocarotenoid biosynthesis.

Background: Crocus sativus is a triploid sterile plant with long red stigmas which form commercial saffron. Saffron is the site for synthesis and accumulation of apocarotenoids like crocin, picrocrin and safranal which are responsible for its color, flavour and aroma making it world's most expensive spice. These compounds are formed by oxidative cleavage of zeaxanthin by carotenoid cleavage dioxygenases.

Synthetic modification of hydroxychavicol by Mannich reaction and alkyne-azide cycloaddition derivatives depicting cytotoxic potential.

Here we report the design, synthesis and lead optimization of hydroxychavicol (1) a high yielding metabolite ubiquitously present in the Piper betel leaves with the significant cytotoxic activity. This is the first report to describe the synthetic strategies of two distinct series of hydroxychavicol by Mannich reaction (2-10) and alkyne-azide cycloaddition (11-20). Furthermore, all the synthesized derivatives along with parent compound were evaluated for their in-vitro cytotoxic and antiproliferative potential in several distinct cancers cell lines.

A general metal-free approach for the stereoselective synthesis of C-glycals from unactivated alkynes.

A novel metal-free strategy for a rapid and α-selctive C-alkynylation of glycals was developed. The reaction utilizes TMSOTf as a promoter to generate in situ trimethylsilylacetylene for C-alkynylation. Thanks to this methodology, we can access C-glycosides in a single step from a variety of acetylenes , i.

Identification and optimization of Escherichia coli GlmU inhibitors: an in silico approach with validation thereof.

Bacterial infections are causing havoc on the populace. Continuous rising of antibiotic resistance in bacteria causes pressing requirement of new drugs and drug therapies that are effective against these multidrug resistance bacteria. GlmU, which is a bifunctional acetyltransferase/uridyltransferase enzyme, is novel target to treat bacterial infections.

Simultaneous quantification of eight bioactive secondary metabolites from Codonopsis ovata by validated high performance thin layer chromatography and their antioxidant profile.

Chemical investigation of Codonopsis ovata resulted in the isolation and identification of β-sitosterol-3-O-glycoside, luteolin, apigenin, gentiacaulein, swertiaperenine, β-sitosterol, taraxeryl-3-acetate, and 3β-acetoxyoleanane-12-one. A rapid, precise, sensitive and validated HPTLC method for simultaneous quantification of these natural products (NPs) was developed on silica-gel 60F254 plate using ternary solvent system, n-hexane:ethyl acetate:formic acid (10.5:3.

Design, synthesis and biological evaluation of β-boswellic acid based HDAC inhibitors as inducers of cancer cell death.

The synthesis and bio-evaluation of naturally occurring boswellic acids (BAs) as an alternate CAP for the design of new HDAC inhibitors is described. All the compounds were screened against a panel of human cancer cell lines to identify leads, which were subsequently examined for their potential to inhibit HDACs. The identified lead compound showed IC50 value of 6μm for HDACs, found to induce G1 cell cycle arrest at significantly low concentration (1μM) and caused significant loss in mitochondrial membrane potential at 5 and 10μM.

Click chemistry inspired synthesis and bioevaluation of novel triazolyl derivatives of osthol as potent cytotoxic agents.

A new series of diverse triazoles linked through the hydroxyl group of lactone ring opened osthol (1) were synthesized using click chemistry approach. All the derivatives were subjected to 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) cytotoxicity screening against a panel of seven different human cancer cell lines viz. colon (colo-205), colon (HCT-116), breast (T47D), lung (NCI-H322), lung (A549), prostate (PC-3) and Skin (A-431) to check their cytotoxic potential.

An investigation of in vitro cytotoxicity and apoptotic potential of aromatic diselenides.

A target synthesis of a library of symmetric aromatic diselenides was attempted with the aim of generating anticancer lead compounds. Out of thirteen screened molecules (1-13) against a panel of human cancer cell lines, compound 8 exhibited highest cell growth inhibition in Human leukemia HL-60 cells with IC50 value of 8 μM. Compound 8 had a good pro-apoptotic potential as evidenced from several apoptotic protocols like DNA cell cycle analysis and monitoring of apoptotic bodies formation using phase contrast and nuclear microscopy with Hoechst 33,258.

A cross-cultural analysis of Jammu, Kashmir and Ladakh (India) medicinal plant use.

Ethnopharmacological Relevance: Jammu & Kashmir (J&K) is a predominantly Himalayan state in the north-western part of India. It has three geographically distinct divisions viz., Jammu, Kashmir and Ladakh, which are immensely rich in their biological and cultural diversity.

Synthesis, characterization and mechanistic-insight into the anti-proliferative potential of PLGA-gemcitabine conjugate.

Gemcitabine, a nucleoside analogue, is used in the treatment of various solid tumors, however, its efficacy is limited by rapid metabolism by cytidine deaminase and fast kidney excretion. In this study, a polymeric conjugate of gemcitabine was prepared by covalent coupling with poly(lactic-co-glycolic) acid (PLGA), in order to improve anticancer efficacy of the drug. The prepared conjugate was characterized by various analytical techniques including FTIR, NMR and mass spectroscopic analysis.

A convergent synthesis of alkyne-azide cycloaddition derivatives of 4-α,β-2-propyne podophyllotoxin depicting potent cytotoxic activity.

A facile synthetic approach to construct the O-propargyl derivatives of 4α and 4β-(1,2,3-triazol-4-yl)-podophyllotoxin (9a-k & 10a-k) and 4'-Demethyl-4'-4β-(1,2,3-triazol-4-yl)-epipodophyllotoxin (12a-d) were synthesized by means of click chemistry. The chemical structures were confirmed by (1)H, (13)C, 2D NMR and HRMS spectral analysis and their cytotoxicities were measured against diverse human cancer cell lines viz. PC-3, PANC-1, COLO-205 and A-549 by MTT assay.

Synthesis and evaluation of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-(2-(4-substitutedpiperazin-1-yl)acetyl)piperazin-1-yl)quinoline-3-carboxylic acid derivatives as anti-tubercular and antibacterial agents.

A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substitutedpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues were synthesized, characterized ((1)H NMR, (13)C NMR and LCMS) and screened for their in vitro anti-tubercular and antibacterial activity. Many of these compounds exhibited MIC values in the range 7.32-136.

Development of a validated UPLC-qTOF-MS/MS method for determination of bioactive constituent from .

An ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-qTOF-MS/MS) method was developed and validated for the simultaneous determination of glycyrrhizin and glycyrrhetic acid. These analytes were separated on a reverse phase C18 column using a mobile phase of acetonitrile:2% acetic acid in water (75:25, v/v) with a flow rate of 200 μL/min. The qTOF-MS was operated under multiple reaction monitoring (MRM) mode using the electrospray ionization (ESI) technique with positive ion polarity.

Synthesis of 3-O-propargylated betulinic acid and its 1,2,3-triazoles as potential apoptotic agents.

Cytotoxic agents from nature are presently the mainstay of anticancer chemotherapy, and the need to reinforce the arsenal of anticancer agents is highly desired. Chemical transformation studies carried out on betulinic acid, through concise 1,2,3-triazole synthesis via click chemistry approach at C-3position in ring A have been evaluated for their cytotoxic potentiation against nine human cancer cell lines. Most of the derivatives have shown higher cytotoxic profiles than the parent molecule.

Diminutive effect on T and B-cell proliferation of non-cytotoxic α-santonin derived 1,2,3-triazoles: a report.

α-Santonin derived new series of 1,2,3-triazoles synthesized through Azide-Alkyne Huisgen 1,3-dipolar cycloaddition reaction between substituted aryl azide and a propargylated α-desmotrosantonin were bio-evaluated for their diminutive effect on ConA induced T-cell and LPS induced B-cell proliferation. Interestingly, most of the synthesized compounds showed better immunosuppressant activity than α-santonin. Triazole derivatives 9, 10, 17, 18, 29, and 30 displayed significant diminutive effect on cell proliferation.