Synthesis, in silico pharmacokinetic analysis and anticancer activity evaluation of benzothiazole-triazole hybrids

409-417Over the past decade, a variety of benzothiazole derivatives have been reported with promising anticancer activity. Benzothiazole and its analogues are capable of acting on a number of molecular targets and thus exerting their anticancer activity. To further develop benzothiazole derivatives as anticancer agents, we attempted to design and synthesize a library of benzothiazole-triazole derivatives. The synthesized hybrid compounds have been selected by National Cancer Institute, USA for the in vitro activity evaluation against 60 human cancer cell lines in a one dose screening panel. Most of the synthesized compounds showed 60-80% growth rate against renal cancer cell line UO-31

Ionic liquids: a versatile medium for palladium-catalyzed reactions

A number of carbon-carbon bond forming reactions in organic chemistry (such as the Heck, Suzuki, Stille, Negishi, Sonogashira coupling etc) are facilitated by catalysis with palladium compounds. An attempt has been made to present a detailed and comprehensive literature collection about the versatility of ionic liquid in conjunction with palladium for various types of reactions

Synthesis and characterization of novel 1,2,3-triazole-linked theophylline and coumarin <i>s</i>-triazines

311-318A series of novel s-triazine-1,2,3-triazole-theophylline and s-triazine-1,2,3-triazole-coumarin generation-0 dendrimers has been synthesized and characterized by FT-IR, 1H and 13C NMR, and mass-spectral methods. Some selected compounds have been evaluated for antibacterial and antifungal activity against a variety of strains and for anti-cancer activity against 60 human cancer cell lines

Comparative mode of action of novel hybrid peptide CS-1a and its rearranged amphipathic analogue CS-2a

Cell selective, naturally occurring, host defence cationic peptides present a good template for the design of novel peptides with the aim of achieving a short length with improved antimicrobial potency and selectivity. A novel, short peptide CS-1a (14 residues) was derived using a sequence hybridization approach on sarcotoxin I (39 residues) and cecropin B (35 residues). The sequence of CS-1a was rearranged to enhance amphipathicity with the help of a Schiffer–Edmundson diagram to obtain CS-2a. Both peptides showed good antibacterial activity in the concentration range 4–16 &#956;g·mL⁻¹ against susceptible as well as drug-resistant bacterial strains, including the clinically relevant pathogens Acenatobacter sp. and methicillin-resistant Staphylococcus aureus. The major thrust of these peptides is their nonhaemolytic activity against human red blood cells up to a high concentration of 512 &#956;g·mL⁻¹. Compared to CS-1a, amphipathic peptide CS-2a showed a more pronounced α-helical conformation, along with a better membrane insertion depth in bacterial mimic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-dipalmitoyl-sn-glycero-3-phospho-(1&#x2032;-rac-glycerol) small unilamellar vesicles. With equivalent lipid-binding affinity, the two peptides assumed different pathways of membrane disruption, as demonstrated by calcein leakage and the results of transmission electron microscopy on model bacterial mimic large unilamellar vesicles. Extending the work from model membranes to intact Escherichia coli cells, differences in membrane perturbation were visible in microscopic images of peptide-treated E. coli. The present study describes two novel short peptides with potent activity, cell selectivity and divergent modes of action that will aid in the future design of peptides with better therapeutic potential

Monocarbonyl Curcuminoids with Improved Stability as Antibacterial Agents against Staphylococcus aureus and Their Mechanistic Studies

Curcumin has been known to possess diverse pharmacological effects at relatively nontoxic doses; however, its therapeutic potential is severely restricted because of its low aqueous solubility and poor stability under physiological conditions. To overcome its limitations, we had previously designed several monocarbonyl curcuminoids by modifying the central β-diketone moiety of curcumin. In this study, the antibacterial activity of 33 curcuminoids from this designed library has been screened, six of which displayed potent antibacterial activity against clinically relevant Staphylococcus aureus. These curcuminoids were found to be very stable at physiological conditions and did not cause any toxicity toward mammalian cells. Mechanistically, out of these six curcuminoids, five caused instant membrane depolarization and were able to permeabilize the bacterial membrane, which could be the reason for their potent bactericidal activity and the sixth one killed staphylococcal cells without damaging the bacterial membrane. Overall, the present work established the staphylocidal potency of six water-soluble, nontoxic curcuminoids, thereby providing an impetus for the development of these lead curcuminoids for therapeutic use against S. aureus

RGO/ZnO nanocomposite: an efficient, sustainable, heterogeneous, amphiphilic catalyst for synthesis of 3-substituted indoles in water

A nanocomposite consisting of reduced graphene oxide and zinc oxide nanoparticles (RGO/ZnO) with unique structural features was developed as an efficient, sustainable, amphiphilic, heterogeneous catalyst for the synthesis of various 3-substituted indoles in water. The catalyst was recycled six times without significant loss in catalytic activity. The higher environmental compatibility and sustainability factors such as smaller E-factor and higher atom economy make the present methodology a true green and sustainable process for the synthesis of various biologically important 3-substituted indoles

Reduced Graphene Oxide Supported Copper Oxide Nanocomposites from a Renewable Copper Mineral Precursor: A Green Approach for Decarboxylative C(sp³)–H Activation of Proline Amino Acid To Afford Value-Added Synthons

A green approach for decarboxylative C­(sp³)–H activation of proline amino acid was accomplished by coupling with aldehydes and alkynes to afford α-alkynylated N-substituted pyrrolidines as value-added synthons using reduced graphene oxide supported copper oxide (RGO@CuO) nanocatalysts. The RGO@CuO nanocomposites were obtained by the impregnation of micrometer-sized malachite spheres, as a renewable and sustainable copper mineral precursor, on the graphene oxide (GO) sheets followed by calcination at 300–450 °C for 5 h. The characterization of as-synthesized composites revealed the generation of monodispersed and uniformly embedded copper oxide (CuO) nanoparticles with sizes ranging from 10 to 15 nm on RGO thin sheets via GO as a support as well as indirect template for dissembling and decomposition of micrometer-sized malachite spheres. The RGO@CuO composites were found to be efficient and robust nanocatalysts compared with CuO nanoparticles (NPs) alone. The present method offers several advantages, such as wide substrate scope, and avoids the usage of excess equivalent of substrates with minimal waste generation (E-factor = 0.24) and high reaction mass efficiency (80.7%), and the nanocatalyst was recycled for five times without significant loss in its activity with a negligible leaching of CuO NPs from RGO sheets

Synthesis of 1,3,4-oxadiazole and imidazo[1,2-a]pyridine based molecular hybrids and their in vitro antituberculosis and cytotoxicity studies

1005-1018A library of novel 1,3,4-oxadiazole substituted imidazo[1,2-a]pyridine based molecular hybrids have been synthesized and evaluated against Mycobacterium tuberculosis H37Rv. Out of 59 compounds synthesized, ten compounds show activity in the range of 3.125-12.5 μM. Compound 8p is found to be most active with MIC99 value of 3.125-6.25 μM. Further, these ten compounds have also been tested for their toxicity against THP-1 cell line and are found to be non-toxic with TC50 value in the range of (10 - >50 μM) concentration