Searching for the Holy Grail - Highly Potent Bridged Endoperoxides for Targeted Cancer Therapy.

The International Agency for Research on Cancer (IARC) recently estimated the global cancer burden in 2050. The statistics are startling, with a 77% hike and 35 million new cancer cases per year. The present discoveries have recommended plant-derived bridged endoperoxides or artemisinin-based semisynthetic analogues as safe, well-tolerated and powerful substitutes that could be effectively utilized as a warhead to fight against global enemies like cancer.

Challenges in cybersecurity: Lessons from biological defense systems.

Defending against novel, repeated, or unpredictable attacks, while avoiding attacks on the 'self', are the central problems of both mammalian immune systems and computer systems. Both systems have been studied in great detail, but with little exchange of information across the different disciplines. Here, we present a conceptual framework for structured comparisons across the fields of biological immunity and cybersecurity, by framing the context of defense, considering different (combinations of) defensive strategies, and evaluating defensive performance.

Detection of Malicious Cloud Bandwidth Consumption in Cloud Computing Using Machine Learning Techniques.

The Internet of Things, sometimes known as IoT, is a relatively new kind of Internet connectivity that connects physical objects to the Internet in a way that was not possible in the past. The Internet of Things is another name for this concept (IoT). The Internet of Things has a larger attack surface as a result of its hyperconnectivity and heterogeneity, both of which are characteristics of the IoT.

TMEDA-Catalyzed Regioselective Decarboalkoxy C-N Bond Formation: A Unified Direct Access to Indolo[2,1-a]isoquinoline and Dibenzopyrrocoline Alkaloids.

An unprecedented TMEDA-catalyzed, regioselective, decarboethoxy direct C-N coupling protocol towards the synthesis of dibenzopyrrocolines 17 a-i and 5,6-dihydroindolo[2,1-a]isoquinoline 15 a-f/18 a-c alkaloids via the identification of N,N,N',N'-tetramethylethylenediamine (TMEDA) as a homogeneous catalyst is reported. The transition-metal-free, TMEDA-catalytic novel protocol is operationally simple and showed a wide range of functional group tolerance and substrate compatibility. The gram-scale application and synthesis of naturally occurring Cryptaustoline (dibenzopyrrocoline) alkaloid, further highlights the importance and versatile nature of the developed protocol.

Implementing Critical Machine Learning (ML) Approaches for Generating Robust Discriminative Neuroimaging Representations Using Structural Equation Model (SEM).

Critical ML or CML is a critical approach development of the standard ML (SML) procedure. Conventional ML (ML) is being used in radiology departments where complex neuroimages are discriminated using ML technology. Radiologists and researchers found that sole decision by the ML algorithms is not accurate enough to implement the treatment procedure.

Biological Evaluation in Resistant Cancer Cells and Study of Mechanism of Action of Arylvinyl-1,2,4-Trioxanes.

1,2,4-trioxane is a pharmacophore, which possesses a wide spectrum of biological activities, including anticancer effects. In this study, the cytotoxic effect and anticancer mechanism of action of a set of 10 selected peroxides were investigated on five phenotypically different cancer cell lines (A549, A2780, HCT8, MCF7, and SGC7901) and their corresponding drug-resistant cancer cell lines. Among all peroxides, only and showed a better P-glycoprotein (P-gp) inhibitory effect at a concentration of 100 nM.

Au nanoparticles decorated ZnO/ZnFeO composite SERS-active substrate for melamine detection.

Surface-enhanced Raman scattering (SERS) based on plasmonic metal nanoparticles and semiconductors has been used as performance-enhancing structures for sensing trace chemicals. We have selected a case of oxide functional oxide organic nanostructure between ZnFeO and ZnO, denoted as ZZF. By decorating such nanostructure with AuNPs, to identify R6G in varying concentrations (10 M - 10 M), an enhancement factor of 1.

Novel halogenated arylvinyl-1,2,4 trioxanes as potent antiplasmodial as well as anticancer agents: Synthesis, bioevaluation, structure-activity relationship and in-silico studies.

Herein, we have synthesized a series of lipophilic, halogenated-arylvinyl-1,2,4-trioxanes 8a-g (28 compounds) and assessed for their in vitro anti-plasmodial activity in Plasmodium falciparum culture using SYBRgreen-I fluorescence assay against chloroquine-resistant Pf INDO and artemisinin-resistant Pf Cam 3.1 (MRA-1240) strains. Alongside, the cell cytotoxic potential of 8a-g has also been determined against the HEK293 cell line in vitro.

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.

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.

Artemisinin-derived antimalarial endoperoxides from bench-side to bed-side: Chronological advancements and future challenges.

According to WHO World Malaria Report (2018), nearly 219 million new cases of malaria occurred and a total no. of 435 000 people died in 2017 due to this infectious disease. This is due to the rapid spread of parasite-resistant strains.

Recent Developments in Natural Product Inspired Synthetic 1,2,4- Trioxolanes (Ozonides): An Unusual Entry into Antimalarial Chemotherapy.

According to WHO "World health statistics 2018", malaria alongside acute respiratory infections and diarrhoea, is one of the major infectious disease causing children's death in between the age of 1-5 years. Similarly, according to another report (2016) malaria accounts for approximately 3.14% of the total disease burden worldwide.

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.

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.