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).

Therapeutic role of NLRP3 inflammasome inhibitors against Alzheimer's disease.

The NLRP3 inflammasome is a multiprotein complex that plays a vital role in regulating inflammatory signaling and the innate immune system. Activation of NLRP3 by accumulation of Aβ leads to its oligomerization and the activation of caspase-1, resulting in the secretion of pro-cytokines such as IL-18 and IL-1β. These pro-cytokines can contribute to cognitive impairment and neurodegeneration.

Targeting cancer using scaffold-hopping approaches: illuminating SAR to improve drug design.

Scaffold hopping is a design approach involving alterations to the core structure of an already bioactive scaffold to generate novel molecules to discover bioactive hit compounds with innovative core structures. Scaffold hopping enhances selectivity and potency while maintaining physicochemical, pharmacodynamic (PD), and pharmacokinetic (PK) properties, including toxicity parameters. Numerous molecules have been designed based on a scaffold-hopping strategy that showed potent inhibition activity against multiple targets for the diverse types of malignancy.

1,2,4,5-Tetraoxane derivatives/hybrids as potent antimalarial endoperoxides: Chronological advancements, structure-activity relationship (SAR) studies and future perspectives.

Malaria is a life-threatening disease that affects tropical and subtropical regions worldwide. Various drugs were used to treat malaria, including artemisinin and derivatives, antibiotics (tetracycline, doxycycline), quinolines (chloroquine, amodiaquine), and folate antagonists (sulfadoxine and pyrimethamine). Since the malarial parasites developed drug resistance, there is a need to develop new chemical entities with high efficacy and low toxicity.

Regiodivergent Cu-Promoted, AcOH-Switchable Distal Versus Proximal Direct Cyanation of 1-Aryl-1-indazoles and 2-Aryl-2-indazoles via Aerobic Oxidative C-H Bond Activation.

A copper-promoted regiodivergent, AcOH-switchable, distal and proximal direct cyanation of -aryl-(1/2)-indazoles via aerobic oxidative C(sp)-H bond activation has been developed. The inclusion or exclusion of AcOH as an additive is the foremost cause for the positional switch in the C-CN bond formation method that results in (C-2')-cyanated 2-aryl-2-indazoles , (C-2')-cyanated 1-aryl-1-indazoles [distal], or C-3 cyanated 2-aryl-2-indazoles [proximal] products in good to excellent yields and showed various functional group tolerance. The cyanide (CN) ion surrogate was generated via the unification of dimethylformamide and ammonium iodide (NHI).

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.

Oxidant-Switched Palladium-Catalyzed Regioselective Mono- versus Bis--Aroylation of 1-Aryl-1-indazoles with Aldehydes via C-H Bond Activation.

A highly efficient oxidant-switched palladium-catalyzed regioselective C-H/C-H cross-dehydrogenative coupling (CDC) for direct mono/bis-aroylation of substituted 1-phenyl-1-indazoles with various substituted aldehydes via C-H bond activation has been developed. In this study, Pd-catalyzed chelation-assisted mono- or bis-aroylation of substituted 1-phenyl1-indazoles depends on the type of oxidant being used for the CDC reaction. While mono--aroylation of substituted 1-phenyl-1-indazole was obtained using dicumylperoxide (DCP) as the oxidant, the bis--aroylation product has been afforded by the use of -butyl hydroperoxide (TBHP).

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.