Anticancer Potential of the S-Heterocyclic Ring Containing Drugs and its Bioactivation to Reactive Metabolites.

Sulfur-containing heterocyclic derivatives have been disclosed for binding with a wide range of cancer-specific protein targets. Various interesting derivatives of sulfur-containing heterocyclics such as benzothiazole, thiazole, thiophene, thiazolidinedione, benzothiophene, and phenothiazine, etc have been shown to inhibit diverse signaling pathways implicated in cancer. Significant progress has also been made in molecular targeted therapy against specific enzymes such as kinase receptors due to potential binding interactions inside the ATP pocket.

Pyrazinacene conjugated polymers: a breakthrough in synthesis and unraveling the conjugation continuum.

Pyrazinacenes are next generation N-heteroacenes and represent a novel class of stable n-type materials capable of accepting more than one electron and displaying intriguing features, including prototropism, halochromism, and redox chromism. Astonishingly, despite a century since their discovery, there have been no reports on the conjugated polymers of pyrazinacenes due to unknown substrate scope and lack of pyrazinacene monomers that are conducive to condensation polymerization. Breaking through these challenges, in this work, we report the synthesis of previously undiscovered and highly coveted conjugated polymers of pyrazinacenes.

Recent Development of Heterocyclic Compounds with Indazole Moiety as Potential Antiparasitic Agents.

Indazole is a vital nitrogen-containing heterocyclic unit in organic and medicinal chemistry research and a helpful precursor molecule for the production of various types of encirclement heterocycles. Indazole analogues are diverse pharmacological agents that can be used to treat a variety of conditions, including cancer, inflammation, infectious diseases, and neurological problems. In fact, the indazole moiety containing inhibitors also showed excellent medicinal properties for the treatment of parasitic diseases.

Fungal Endophytes: A Storehouse of Bioactive Compounds.

Fungal endophytes are the microbial adaptations that usually enter the plant tissues during their life cycle without harming the host plants. They are found everywhere on earth and generally depend on the hosts by developing various symbiotic relationships, like mutualism, hostility, and parasitism on rare occasions, leading to the growth and rise in the nutrient content of the hosts. Endophytes can develop tolerance in host organisms against the stresses induced by either living or non-living agents.

Molecular tetrominoes: selective masking of the donor π-face to control the configuration of donor-acceptor complexes.

Understanding the doping mechanism in organic semiconductors and generating molecular design rules to control the doping process are crucial for improving the performance of organic electronics. Even though controlling the location and orientation of the dopant along the semiconductor backbone is an important step in the doping mechanism, studies in this direction are scarce as it is a challenging task. To address this, herein, we incorporated π-face masked (strapped) units in 1,4-bis(phenylethynylene)benzene (donor) to control the acceptor (dopant) location along the trimer, donor-acceptor binding strength, and acceptor ionization.

Anti-inflammatory Potential of GSK-3 Inhibitors.

Glycogen synthase kinase-3 (GSK-3) is a protein kinase containing threonine or serine amino acid residues. GSK-3 was first discovered in 1980 as a regulatory protein kinase, Glycogen synthase (GS) enzyme, which is responsible for the conversion of glycogen from glucose with the help of uridine diphosphate glucose (UDP-Glu) residue. GSK-3 has two isoforms present in human beings, namely GSK-3 α (serine residue at 21 position) and GSK-3 β (serine residue at 9 position).

Network pharmacology of AYUSH recommended immune-boosting medicinal plants against COVID-19.

The Ministry of AYUSH recommended the use of a decoction of the mixture of , , , and as a preventive measure by boosting the immunity against the severity of infection caused by a novel coronavirus (COVID-19). The present study aimed to identify the probable modulated pathways by the combined action of AYUSH recommended herbal tea and golden milk formulation as an immune booster against COVID-19. Reported phytoconstituents of all the medicinal plants were retrieved from the ChEBI database, and their targets were predicted using DIGEP-Pred.

In silico analysis and identification of promising hits against 2019 novel coronavirus 3C-like main protease enzyme.

The recent outbreak of the 2019 novel coronavirus disease (COVID-19) has been proved as a global threat. No particular drug or vaccine has not yet been discovered which may act specifically against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and causes COVID-19. For this highly infectious virus, 3CL-like main protease (3CL) plays a key role in the virus life cycle and can be considered as a pivotal drug target.

Oxidative cyanation of 2-oxindoles: formal total synthesis of (±)-gliocladin C.

Efficient oxidative direct cyanations of 3-alkyl/aryl 2-oxindoles using Cyano-1,2-BenziodoXol-3(1H)-one (CBX) (2a) have been reported under 'transition metal-free' conditions to synthesize a wide variety of 3-cyano 3-alkyl/aryl 2-oxindoles sharing an all-carbon quaternary center under additive-free conditions. The application of this process is shown by the formal total synthesis of (±)-gliocladin C (11c) in a few steps.

A catalytic N-deacylative alkylation approach to hexahydropyrrolo[2,3-b]indole alkaloids.

A versatile unprecedented strategy to diversely functionalized hexahydropyrrolo[2,3-b]indole alkaloids is described in high chemical yields. The synthesis features a key Pd(0)-catalyzed deacylative alkylation of N-acyl 3-substituted indoles using only 1 mol% of Pd(PPh3)4. The scope of this methodology is further defined in the asymmetric synthesis of pyrroloindolines using a diastereoselective approach.

Pd(0)-Catalyzed Chemoselective Deacylative Alkylations (DaA) of N-Acyl 2-Oxindoles: Total Syntheses of Pyrrolidino[2,3- b]indoline Alkaloids, (±)-Deoxyeseroline, and (±)-Esermethole.

We report an efficient Pd(0)-catalyzed deacylative allylation of N-acyl 3-substituted 2-oxindoles via the coupling of in situ generated nucleophiles (3 and 4) with allyl electrophiles for the synthesis of a variety of 2-oxindoles with C3-quaternary centers. Gratifyingly, this alkylation process is found to be highly chemoselective in nature, where a C-C bond formation is completely predominant over a C-N bond formation. A variety of key intermediates were synthesized utilizing an aforementioned methodology.

Novel Phospholipid-Protein Conjugates Allow Improved Detection of Antibodies in Patients with Autoimmune Diseases.

Reliable measurement of clinically relevant autoimmune antibodies toward phospholipid-protein conjugates is highly desirable in research and clinical assays. To date, the development in this field has been limited to the use of natural heterogeneous antigens. However, this approach does not take structural features of biologically active antigens into account and leads to low reliability and poor scientific test value.

Enzyme-Free Detection of Mutations in Cancer DNA Using Synthetic Oligonucleotide Probes and Fluorescence Microscopy.

Background: Rapid reliable diagnostics of DNA mutations are highly desirable in research and clinical assays. Current development in this field goes simultaneously in two directions: 1) high-throughput methods, and 2) portable assays. Non-enzymatic approaches are attractive for both types of methods since they would allow rapid and relatively inexpensive detection of nucleic acids.

Synthesis of Phospholipid-Protein Conjugates as New Antigens for Autoimmune Antibodies.

Copper(I)-catalyzed azide-alkyne cycloaddition, or CuAAC click chemistry, is an efficient method for bioconjugation aiming at chemical and biological applications. Herein, we demonstrate how the CuAAC method can provide novel phospholipid-protein conjugates with a high potential for the diagnostics and therapy of autoimmune conditions. In doing this, we, for the first time, covalently bind via 1,2,3-triazole linker biologically complementary molecules, namely phosphoethanol amine with human β2-glycoprotein I and prothrombin.

Spermicidal and contraceptive potential of desgalactotigonin: a prospective alternative of nonoxynol-9.

Crude decoction of Chenopodium album seed showed spermicidal effect at MIC 2 mg/ml in earlier studies. Systematic isolation, characterization and evaluation revealed that the major metabolite Desgalactotigonin (DGT) is the most effective principle in both in vitro and in vivo studies. The in vitro studies comprises (a) rat and human sperm motility and immobilizing activity by Sander-Cramer assay; (b) sperm membrane integrity was observed by HOS test and electron microscopy; (c) microbial potential was examined in Lactobacillus broth culture, and (d) the hemolytic index was determined by using rat RBCs.

Regio- and stereoselective synthesis of a library of bioactive dispiro-oxindolo/acenaphthoquino andrographolides via 1,3-dipolar cycloaddition reaction under microwave irradiation.

Dispiro-pyrrolidino/pyrrolizidino fused oxindoles/acenaphthoquinones have been derived from andrographolide via azomethine ylide cycloaddition to the conjugated double-bond under microwave (MW) irradiation. The reactions are chemo-, stereo-, and regioselective in nature. Change in amino acid from sarcosine/N-benzyl glycine to l-proline changes the regiochemistry.

Discovery of safe and orally effective 4-aminoquinaldine analogues as apoptotic inducers with activity against experimental visceral leishmaniasis.

Novel antileishmanials are urgently required to overcome emergence of drug resistance, cytotoxic effects, and difficulties in oral delivery. Toward this, we investigated a series of novel 4-aminoquinaldine derivatives, a new class of molecules, as potential antileishmanials. 4-Aminoquinaldine derivatives presented inhibitory effects on L.

Overcoming multidrug resistance (MDR) in cancer in vitro and in vivo by a quinoline derivative.

Multidrug resistance (MDR) mediated by the over expression of drug efflux protein P-glycoprotein (P-gp) is one of the major impediments to successful treatment of cancer. P-gp acts as an energy-dependent drug efflux pump and reduces the intracellular concentration of structurally unrelated drugs inside the cells. Therefore, there is an urgent need for development of new compound that are less toxic and effective against drug resistance in cancer.

Amberlite-IRA-402 (OH) ion exchange resin mediated synthesis of indolizines, pyrrolo [1,2-a] quinolines and isoquinolines: antibacterial and antifungal evaluation of the products.

A number of indolizines and pyrrolo[1,2-a]quinolines/isoquinolines were prepared from phenacyl pyridinium, quinolinium and isoquinolinium salts derived from the reaction of the heterocycles with 2-bromo acetophenone with alkynes and alkenes using amberlite-IRA-402 (OH) ion exchange resin as the base. Antibacterial and antifungal studies were carried out against thirteen bacterial and four fungal strains, which revealed that three derivatives (4a, 4b, 7a) out of fifteen are effective against all the thirteen strains and one derivative, 10, showed dual antibactericidal and antifungal efficacy.

Efficient synthesis of 3,3-diheteroaromatic oxindole analogues and their in vitro evaluation for spermicidal potential.

Syntheses of 3,3-diheteroaromatic oxindole derivatives has been achieved by coupling indole-2,3-dione (isatin) with differently substituted indoles and pyrrole in presence of I(2) in i-PrOH. The in vitro spermicidal potentials and the mode of spermicidal action of the synthesized analogues were evaluated and the derivative, 3,3-bis (5-methoxy-1H-indol-3-yl) indolin-2-one (3d) exhibited most significant activity.