SIRT6 and COX-2 are oncogenes target that promote the expression of proinflammatory and pro-survival proteins through a signaling pathway, which leads to increased survival and proliferation of tumor cells. However, COX-2 also suppresses skin tumorigenesis and their relationship with SIRT6, making it an interesting target for the discovery of drugs with anti-inflammatory and anti-cancer properties. Herein, we studied the interaction of thieno[3,2-c]pyran analogs and RONS species with SIRT6 and COX-2 through the use of molecular docking and molecular dynamic simulations. Molecular docking studies revealed the importance of hydrophobic and hydrophilic amino acid residues for the stability. The molecular dynamics study examined conformational changes in the enzymes caused by the binding of the substrates and how those changes affected the stability of the protein-drug complex. The average RMSD values of the backbone atoms in compounds 6 and 10 were calculated from 1000 ps to 10000 ps and were found to be 0.13 nm for both compounds. Similarly, the radius of gyration values for compounds 6 and 10 were found to be 1.87 ± 0.03 nm and 1.86 ± 0.02 nm, respectively. The work presented here, will be of great help in lead identification and optimization for early drug discovery.

Copper nanoparticles (CuNPs) were synthesized under ambient temperature by wet chemical method and evaluated their antibacterial activity by the means of well diffusion method. In this study, we have analyzed the effect of NaBH 4 concentration on the synthesis of CuNPs. Surface plasmon resonance (SPR) was occurred at 575 nm. Scanning electron microscopy micrographs shows CuNPs have spherical morphology with size range of 20-40 nm. Dynamic light scattering (DLS) showed the particles size increases with the concentration of reducing agent NaBH 4 . As prepared, CuNPs, demonstrated antibacterial activity against E. coli, Staphylococcus aureus and Pseudomonas aeruginosa. The potential mechanism of antibacterial activity was discussed with diagrammatic representation.

This article describes the identification of 1-(2-hydroxyethyl)-piperazine as a new, cost-effective, highly efficient organocatalyst, which promotes both inter-and intra-molecular direct C( sp 2 )−H arylations of unactivated arenes in the presence of potassium tert-butoxide. While the inter-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 intra-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 inter-and intra-molecular direct arylations simultaneously in a single pot. The mechanistic studies confirmed the involvement of aryl radical anions and proceeded via a single-electron-transfer (SET) mechanism. The large substrate scope, high functional group tolerance, competition experiments, gram-scale synthesis, and kinetic studies further highlight the importance and versatile nature of the methodology as well as the compatibility of the new catalyst. To the best of our knowledge, this is the first report on any organocatalyst that reported detailed investigations of both inter-and intra-molecular direct C( sp 2 )−H arylations of unactivated arenes in a single representation.

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 via sonogashira type coupling followed by substrate-controlled 5-exo-dig or 6-endo-dig cyclization reaction, respectively. This one pot coupling involves reaction of substituted 2-halobenzoic acid with meta/para-substituted and ortho-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. The competition experiments and gram-scale synthesis further highlight the importance and versatility of the methodology. The proposed mechanistic pathways illustrate that the regioselectivity is substantially being controlled by the substituent(s) present on the acetylenic phenyl ring.

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 (IC50=0.051 μM; SI=589.41) and 8 m (IC50=0.059 μM; SI=55.93) showed 11‐fold and >9‐fold more potent antiplasmodial activity, respectively, as compared to chloroquine (IC50=0.546 μM; SI=36.63). Different in silico docking studies performed on many target proteins revealed that the most active arylvinyl‐1,2,4‐trioxanes (8 g and 8 m) showed dihydrofolate reductase (DHFR) binding affinities on a par with those of chloroquine and artesunate. The in vitro cytotoxic potentials of 8 a–p were also evaluated against human lung (A549) and liver (HepG2) cancer cell lines along with immortalized normal lung (BEAS‐2B) and liver (LO2) cell lines. Following screening, five derivatives viz. 8 a, 8 h, 8 l, 8 m and 8 o (IC50=1.65–31.7 μM; SI=1.08–10.96) were found to show potent cytotoxic activity against (A549) lung cancer cell lines, with selectivity superior to that of the reference compounds artemisinin (IC50=100 μM), chloroquine (IC50=100 μM) and artesunic acid (IC50=9.85 μM; SI=0.76). In fact, the most active 4‐naphthyl‐substituted analogue 8 l (IC50=1.65 μM; SI >10) exhibited >60 times more cytotoxicity than the standard reference, artemisinin, against A549 lung cancer cell lines. In silico docking studies of the most active anticancer compounds, 8 l and 8 m, against EGFR were found to validate the wet lab results. In summary, a new series of functionalized aryl‐vinyl‐1,2,4‐trioxanes (8 a–p) has been shown to display dual potency as promising antiplasmodial and anticancer agents.

For the first time, a series of highly potent natural product inspired substituted (Z)-3benzylideneisobenzofuran-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 50 = 4.57 µg/mL) and aspirin (ic 50 = 21.34 µg/mL), as standard references, respectively. In this study, compounds 28f-g, 28k-l and 28q have shown high order of in vitro antioxidant activity. Infact, 28f and 28k were found to show 10-folds and 8-folds more antioxidant activity than ascorbic acid, respectively and was found to be the most active analogues of the series. Similarly, Compounds 28c-g, 28k-l, 28o and 28q-t were recognized as highly potent antiplatelet agents (upto 6-folds) than aspirin. furthermore, in silico studies of the most active antioxidants 28f, 28k and 28l and very active antiplatelet molecules 28f, 28k, 28l and 28s were carrying out for the validation of the biological results. This is the first detailed study of the discovery of several (Z)-3-benzylideneisobenzofuran-1(3H)-ones as highly potent antioxidants and antiplatelet agents. Isobenzofuran-1(3 H)-one, commonly known as "phthalide" is found in many naturally-occurring and pharmaceuticals important molecules 1. This benzo-fused heterocyclic class of compounds are blended with several pharmacological properties such as anti-tumor 2 , anti-HIV 3 , anti-allergic 4 , antifungal 5 , antidiabetic 6 , antispasmodic 7 , anti-inflammatory 8 , pesticidal 9 , COX-2 inhibitor 10 , insecticidal 11 , anti-microbial 12 , herbicidal 13 , and anti-cancer 14 etc. Several naturally occurring as well as synthetic molecules having isobenzofuran-1(3H)-ones have also been classified as promising antioxidants 1-7 (Fig. 1) 15-18. Similarly, several natural and synthetic molecules 7-15 show promising platelet aggregation inhibitors 15 (Fig. 1). Relevant to the present study, natural product inspired isobenzofuran-1(3 H)-ones are known to be potential antioxidant (7) and antiplatelet agents (7, 12-15) 15,19-21. Earlier, Teng and his co-workers carried out extensive platelet aggregation inhibitory studies on butylidenephthalide 7 triggered by various inducers such as Arachidonic acid (AA), Adenosine diphosphate (ADP), platelet activation factor (PAF), etc. as well as the inhibition of thromboxane B2 (TXB2) formation caused by AA, collagen, ionophore A23187 and thrombin 20. In this study, 7 showed significantly higher inhibitory

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A Bu4NI-Catalyzed, DTBP-promoted, regioselective C(sp2)–C(sp3) cross dehydrogenative coupling (CDC) protocol for the direct C-3 benzylation of 2H-indazoles is reported. The metal-free protocol is operationally simple and proceeds mechanistically via the...