Novel stilbene-chalcone (S-C) hybrids were synthesized via a sequential Claisen-Schmidt-Knoevenagel-Heck approach and evaluated for antiplasmodial activity in in vitro red cell culture using SYBR Green I assay. The most potent hybrid (11) showed IC(50) of 2.2, 1.4, and 6.4 μM against 3D7 (chloroquine sensitive), Indo, and Dd2 (chloroquine resistant) strains of Plasmodium falciparum, respectively. Interestingly, the respective individual stilbene (IC(50) > 100 μM), chalcone (IC(50) = 11.5 μM), or an equimolar mixture of stilbene and chalcone (IC(50) = 32.5 μM) were less potent than 11. Studies done using specific stage enriched cultures and parasite in continuous culture indicate that 11 and 18 spare the schizont but block the progression of the parasite life cycle at the ring or the trophozoite stages. Further, 11 and 18 caused chromatin condensation, DNA fragmentation, and loss of mitochondrial membrane potential in Plasmodium falciparum, thereby suggesting their ability to cause apoptosis in malaria parasite.

Ionic liquids have been found to provide a new platform for metal-and quinoline-free decarboxylation of various N-heteroaryl and aryl carboxylic acids under microwave irradiation in aqueous condition. The method was found to possess a wide substrate scope towards the synthesis of various pharmacologically and industrially important aromatic compounds including indoles, styrenes, stilbenes, and nitro-or hydroxyarene derivatives. The decarboxylation of indole and a-phenylcinnamic acids proceeded well without addition of any catalyst in neat 1-hexyl-3-methylimidazolium bromide ([hmim]Br) and 1-methylimidazolium p-toluenesulfonic acid ([Hmim]PTSA), respectively, while addition of a mild base like aqueous sodium hydrogen carbonate (NaHCO 3 ) to [hmim]Br further improved the decarboxylation of hydroxylated cinnamic and aromatic acid substrates. The developed methodology not only precludes the usage of toxic metal/quinoline and harsh organic bases but also offers several inherent benefits like recyclability of reagent system, reduction in waste and hazards, short reaction time besides ease of product recovery.

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An effective endocrine therapy for breast cancer is to selectively and effectively degrade the estrogen receptor (ER). Up until now, there have been largely only two molecular scaffolds capable of doing this. In this study, we have developed new classes of scaffolds that possess selective estrogen receptor degrader (SERD) and ER antagonistic properties. These novel SERDs potently inhibit MCF-7 breast cancer cell proliferation and the expression of ER target genes, and their efficacy is comparable to Fulvestrant. Unlike Fulvestrant, the modular protein-targeted chimera (PROTAC)-type design of these novel SERDs should allow easy diversification into a library of analogs to further fine-tune their pharmacokinetic properties including oral availability. This work also expands the pool of currently available PROTAC-type scaffolds that could be beneficial for targeted degradation of various other therapeutically important proteins.

Productivity of rice is adversely affected by salinity and water logging stresses in coastal zones, and affected areas are progressively expanding as consequences of climate change and overexploitation of natural resources to meet the needs of increasing populations. Several varieties were developed and commercialized in this region in recent years, including some salt and stagnant flood (SF, medium deep, 25-50 cm water depth) tolerant varieties. However, suitability of these varieties based on adaptation to local conditions across the region and farmers" preferences have not been sufficiently evaluated. Genotype by environment analysis leads to identification of varieties with stable performance, or suitability to specific regions. Two

A mild and efficient, ionic-liquid-assisted, green protocol for the dehydration of benzyl alcohols into the corresponding (E)-arylalkenes under microwave irradiation has been developed. The method utilizes a neutral and recyclable ionic liquid (1-hexyl-3-methylimidazolium bromide) as a reagent and solvent to cleanly provide a wide range of olefins without

Toll-like receptors (TLRs) recognize various pathogen- and host tissue-derived molecules and initiate inflammatory immune responses. Exaggerated or prolonged TLR activation, however, can lead to etiologically diverse diseases, such as bacterial sepsis, metabolic and autoimmune diseases, or stroke. Despite the apparent medical need, no small-molecule drugs against TLR pathways are clinically available. This may be because of the complex signaling mechanisms of TLRs, which are governed by a series of protein-protein interactions initiated by Toll/interleukin-1 receptor homology domains (TIR) found in TLRs and the cytoplasmic adaptor proteins TIRAP and MyD88. Oligomerization of TLRs with MyD88 or TIRAP leads to the recruitment of members of the IRAK family of kinases and the E3 ubiquitin ligase TRAF6. We developed a phenotypic drug screening system based on the inducible homodimerization of either TIRAP, MyD88, or TRAF6, that ranked hits according to their hierarchy of action. From a bioactive compound library, we identified methyl-piperidino-pyrazole (MPP) as a TLR-specific inhibitor. Structure-activity relationship analysis, quantitative proteomics, protein-protein interaction assays, and cellular thermal shift assays suggested that MPP targets the TIR domain of MyD88. Chemical evolution of the original MPP scaffold generated compounds with selectivity for distinct TLRs that interfered with specific TIR interactions. Administration of an MPP analog to mice protected them from TLR4-dependent inflammation. These results validate this phenotypic screening approach and suggest that the MPP scaffold could serve as a starting point for the development of anti-inflammatory drugs.

Tandem reactions that involve chemoselective Knoevenagel/Perkin condensation-decarboxylation-Heck/Suzuki coupling or Heck-aldol sequences have been achieved. This enabled the first concise and efficient synthesis of several important hydroxy-functionalized compound classes, such as stilbene-cinnamoyl hybrids (potent protein tyrosine phosphatase1B inhibitors), cinnamoyl-cinnamic acid hybrids, asymmetric distyrylbenzenes, and biarylstyrenes. Previously reported synthesis require multiple steps and protection/deprotection manipulations.