N-Arylsulfonylated C-Homoaporphines as a New Class of Antiplatelet and Antimicrobial Agents.

A series of novel N-arylsulfonylated C-homoaporphine alkaloids were synthesized under microwave irradiation and evaluated for their antiplatelet and antimicrobial activities. Among the series, compounds , , , , , , , , and demonstrated highly potent (∼3-fold) platelet aggregation inhibitory activity than acetylsalicylic acid (IC = 21.34 μg/mL).

Discovery of Natural Product Inspired 3-Phenyl-1H-isochromen-1-ones as Highly Potent Antioxidant and Antiplatelet Agents: Design, Synthesis, Biological Evaluation, SAR and In Silico Studies.

Background: Several natural/synthetic molecules having a structure similar to 1H-isochromen- 1-ones have been reported to display promising antioxidants and platelet aggregation inhibitory activity. Isocoumarin (1H-2-benzopyran-1-one) skeleton, either whole or as a part of the molecular framework, has been explored for its antioxidant or antiplatelet activities.

Introduction: Based on the literature, a new prototype, i.

Organocatalyst in Direct C()-H Arylation of Unactivated Arenes: [1-(2-Hydroxyethyl)-piperazine]-Catalyzed -/-molecular C-H Bond Activation.

This article describes the identification of 1-(2-hydroxyethyl)-piperazine as a new, cost-effective, highly efficient organocatalyst, which promotes both - and -molecular direct C()-H arylations of unactivated arenes in the presence of potassium butoxide. While the -molecular C-H arylation of unactivated benzenes with aryl halides (Ar-X; X = I, Br, Cl) toward biaryl syntheses underwent smoothly in the presence of only 10 mol % organocatalyst, the -molecular C-H arylation catalytic system composed of 40 mol % each of the catalyst and the additive (4-dimethylaminopyridine (DMAP)). The novel catalyst was also able to perform both - and -molecular direct arylations simultaneously in a single pot.

Design, Synthesis, Structure-Activity Relationship and Docking Studies of Novel Functionalized Arylvinyl-1,2,4-Trioxanes as Potent Antiplasmodial as well as Anticancer Agents.

A novel series of synthetic functionalized arylvinyl-1,2,4-trioxanes (8 a-p) has been prepared and assessed for their in vitro antiplasmodial activity against the chloroquine-resistant Pf INDO strain of Plasmodium falciparum by using a SYBR green-I fluorescence assay. Compounds 8 g (IC =0.051 μM; SI=589.

Microwave-assisted modified synthesis of C-analogues of naturally occurring methylxanthines: Synthesis, biological evaluation and their practical applications.

An efficient, microwave-assisted, oxidant-interceded, transition-metal-free, cross-dehydrogenative C-C coupling of C-Caffeine 2/Theobromine 3/theophylline 4 with substituted aliphatic alcohols 11a-lvia CH bond activation for the preparation of series of substituted C-(hydroxymethyl) Caffeine 12a-l/theobromine 13a-c/theophylline 14a-b has been developed using microwave irradiation upto 98% yield. The reaction proceeds smoothly in the presence of tert-butyl hydroperoxide (TBHP) under solvolysis condition at 120 °C for 20 min to corresponding substituted C-(hydroxymethyl)-methylxanthine derivatives in good to excellent yields. The good substrate scope, control experiments, gram-scale synthesis, and practical synthetic transformations further highlights the practicality of this methodology.

Synthesis, Bioevaluation, Structure-Activity Relationship and Docking Studies of Natural Product Inspired (Z)-3-benzylideneisobenzofuran-1(3H)-ones as Highly Potent antioxidants and Antiplatelet agents.

For the first time, a series of highly potent natural product inspired substituted (Z)-3-benzylideneisobenzofuran-1(3H)-ones 28a-t, embraced with electron-withdrawing groups (EWG) and electron-donating groups (EDG) at site I and site II, were prepared and assessed for their in vitro antioxidant activities (DPPH free radical scavenging assay) and arachidonic acid (AA)-induced antiplatelet activities using ascorbic acid (IC = 4.57 µg/mL) and aspirin (IC = 21.34 µg/mL), as standard references, respectively.

AgO nanoparticle-catalyzed substrate-controlled regioselectivities: direct access to 3-ylidenephthalides and isocoumarins.

Herein, we disclose the first example of an efficient, silver oxide nanoparticle-catalyzed, direct regioselective synthesis of 3-ylidenephthalides 11-16 and isocoumarins 17-20 sonogashira type coupling followed by substrate-controlled 5--dig or 6--dig cyclization reaction, respectively. This one pot coupling involves reaction of substituted 2-halobenzoic acid with /-substituted and -substituted terminal alkynes, which proceeded in a regioselective manner resulting in the formation of 3-ylidenephthalides or isocoumarins, respectively, in excellent yields (up to 95%) with complete Z-selectivity. This protocol features relatively broad substrate scope, mild conditions, operational simplicity, and is favourable with aromatic/alicyclic terminal alkynes.

Inverse docking based screening and identification of protein targets for Cassiarin alkaloids against .

Various reports have shown Cassiarin alkaloids, selective activities against various strains of with low cytotoxicity, which indicates their possible candidature as antimalarial drug. However, poor recognition of their protein targets and molecular binding behaviour, certainly limits their exploration as antimalarial drug candidature. To address this, we utilises inverse screening, based on three different docking methodologies in order to find their most putative protein targets.

Efficacious cellular codelivery of doxorubicin and EGFP siRNA mediated by the composition of PLGA and PEI protected gold nanoparticles.

This study reports the simultaneous delivery of EGFP siRNA and the chemotherapeutic drug, doxorubicin by means of the composition that results from the electrostatic interaction between positively charged siRNA-complexes of gold nanoparticles (AuNPs) capped with PEI, 25kDa (P25-AuNPs) and negatively charged carboxymethyl cellulose formulated PLGA nanoparticles loaded with doxorubicin. The nanoparticles and their facile interaction were studied by means of dynamic light scattering (DLS), zeta potential, transmission electron microscopic (TEM) measurements. The flow cytometric and confocal microscopic analysis evidenced the simultaneous internalization of both labelled siRNA and doxorubin into around 55% of the HeLa cancer cell population.

New orally active diphenylmethyl-based ester analogues of dihydroartemisinin: Synthesis and antimalarial assessment against multidrug-resistant Plasmodium yoelii nigeriensis in mice.

A new series of ester analogues of artemisinin 8a-f, incorporating diphenylmethyl as pharmacologically privileged substructure, and 8g-j have been prepared and evaluated for their antimalarial activity against multidrug-resistant (MDR) Plasmodium yoelii nigeriensis in Swiss mice via oral route. These diphenylmethyl-based ester analogues 8a-f were found to be 2-4 folds more active than the antimalarial drugs β-arteether 4 and artesunic acid 5. Ester 8a, the most active compound of the series, provided complete protection to the infected mice at 24 mg/kg × 4 days as well as 12 mg/kg × 4 days, respectively.