Synthesis, antimicrobial and cytotoxicity studies of novel undecenoic acid-based triazolothiadiazole derivatives

420-430In the present study, synthesis, antimicrobial and cytotoxic activity studies of 3,6-disubstituted-[1,2,4]triazolo [3,4-b][1,3,4]thiadiazole series compounds have been carried out. Compounds 6d, 6i, 6k, 6p, 6q, 6r, 6s and 6t exhibit promising activity with MIC value of 3.9 μg/mL against some of the tested bacterial strains. Compounds 6r and 6s consistently show promising minimum bactericidal concentration activity with MBC value of 7.8 μg/mL against Staphylococcus aureus MTCC 96 strain. Cytotoxic evaluation study claims that most of the compounds exhibit significant cytotoxicity against all the studied cancer cell lines. Particularly, compounds 6c, 6k, 6l, 6n and 6t against HeLa cell line and compounds 6c and 6h against B16-F10 cell line exhibit promising activities with IC50 values ranging from 6.34 to 9.99 μM. Further, most of the compounds are non-toxic against Chinese hamster ovary cell (CHO-K1) normal cell

Optimization of Linear Arrays using Modified Social Group Optimization Algorithm

354-359In this paper, optimization of the linear array (LA) antenna is performed using modified social group optimization algorithm (SGOA). First step of the work involves in transforming the electromagnetic engineering problem to an optimization problem which is completely described in terms of objectives. Linear array synthesis is inherently considered as a multi-attribute problem. The pattern synthesis of LA is carried out with several objectives involving sidelobe level (SLL), beam-width (BW) and desired nulls. The SLL suppression with BW constraint is considered as first objective of this work and the results are compared with several evolutionary computing algorithms like ant lion (ALO), grey wolf (GWO) and root-runner (RRA). Following this, the MSGOA is further used to synthesise null patterns in which the pattern is completely described in terms of nulls with SLL and BW as constraints. The entire simulation-based experimentation is performed using Matlab® on i5 computing system

Synthesis, cytotoxic evaluation of substituted cinnamic-based 1,2,4-triazolo thiadiazoles

475-481In an attempt to find a new class of cytotoxic agents, a series of 3,6-disubstituted-[1,2,4] triazolo[3,4-b] [1,3,4]thiadiazoles have been synthesized using undecenoic acid and various cinnamic acids. The structures of the synthesized compounds have been confirmed using 1H and 13C NMR, IR and mass spectroscopy. The prepared compounds have been evaluated for their in vitro cytotoxic activities against four human cancer cell lines namely, HeLa, B16-F10, SKOV3, MCF7 and CHO-K1 Normal Cell line using MTT assay. Compounds 6a and 6h show promising activity against HeLa (IC50 value 8.92µM) and SKOV3 cell lines (IC50 value 9.43 µM). Majority of the compounds show significant activities against HeLa cell line with the IC50 values ranging from 8.92 to 13.44 μM. All the compounds show good activity against SKOV3 cell line with the IC50 values ranging from 9.43 to 19.34 μM. Majority of the compounds are non toxic towards the Chinese hamster ovary (CHO-K1) normal cell line

Synthesis, antimicrobial and cytotoxicity studies of novel undecenoic acid-based triazolothiadiazole derivatives

In the present study, synthesis, antimicrobial and cytotoxic activity studies of 3,6-disubstituted-[1,2,4]triazolo [3,4-b][1,3,4]thiadiazole series compounds have been carried out. Compounds 6d, 6i, 6k, 6p, 6q, 6r, 6s and 6t exhibit promising activity with MIC value of 3.9 µg/mL against some of the tested bacterial strains. Compounds 6r and 6s consistently show promising minimum bactericidal concentration activity with MBC value of 7.8 µg/mL against Staphylococcus aureus MTCC 96 strain. Cytotoxic evaluation study claims that most of the compounds exhibit significant cytotoxicity against all the studied cancer cell lines. Particularly, compounds 6c, 6k, 6l, 6n and 6t against HeLa cell line and compounds 6c and 6h against B16-F10 cell line exhibit promising activities with IC50 values ranging from 6.34 to 9.99 μM. Further, most of the compounds are non-toxic against Chinese hamster ovary cell (CHO-K1) normal cell

Synthesis and cytotoxic evaluation of undecenoic acid-based oxime esters

1015-1022A series of undecenoic acid-based aldoxime esters have been synthesized using various substituted benzaldehydes and undecenoic acid. These oxime esters have been evaluated for their cytotoxic activities against HeLa, B16-F10, SKOV3, MCF7 and CHO-K1 normal cell line using MTT assay. Most of the synthesized compounds exhibit cytotoxicity. Particularly, 2,3-dimethoxy (IC50 value 12.48µM) and 3-methoxy (IC50 value 13.58µM) derivatives exhibit promising activities against SKOV3 cell lines. All the synthesized compounds are non-toxic towards the Chinese hamster ovary (CHO-K1) normal cell line

Comparative study of transdermal drug delivery systems of resveratrol: high efficiency of deformable liposomes

Trans-resveratrol (3, 5, 4′ trihydroxystilbene, RSV) is a natural compound that shows antioxidant, cardioprotective, anti-inflammatory and anticancer properties. The transdermal, painless application of RSV is an attractive option to other administration routes owing to its several advantages like avoiding gastrointestinal problems and first pass metabolism. However, its therapeutic potential is limited by its low solubility and low stability in water and the reduced permeability of stratum corneum. To overcome these inconveniences the encapsulation of this compound in a drug delivery system is proposed here. In order to find the best carrier for transdermal application of RSV various liposomal nanoparticulate carriers like conventional liposomes (L-RSV), deformable liposomes (LD-RSV), ultradeformable liposomes (LUD-RSV) and ethosomes (Etho-RSV) were assayed. Transmission electron microscopic (TEM) and dynamic light scattering (DLS) studies were performed to analyze the surface morphology of these carriers. Structural characterization for these formulations was performed by confocal Raman spectroscopy. The spectroscopic results were analysed in conjunction with calorimetric data to identify the conformational changes and stability of formulations in the different nanoparticles induced by the presence of RSV. Comparison of the results obtained with the different carrier systems (L-RSV, LD-RSV, LUD-RSV and Etho-RSV) revealed that the best RSV carrier was LD-RSV. The increase in the fluidity of the bilayers in the region of the hydrophobic chains of the phospholipid by ethanol probably facilitates the accommodation of the RSV in the bilayer and contributes to the improved encapsulation of RSV without affecting the mobility of this carrier.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

P-glycoprotein Mediated Efflux Limits Substrate and Drug Uptake in a Preclinical Brain Metastases of Breast Cancer Model

The blood-brain barrier (BBB) is a specialized vascular interface that restricts the entry of many compounds into brain. This is accomplished through the sealing of vascular endothelial cells together with tight junction proteins to prevent paracellular diffusion. In addition, the BBB has a high degree of expression of numerous efflux transporters which actively extrude compounds back into blood. However, when a metastatic lesion develops in brain the vasculature is typically compromised with increases in passive permeability (blood-tumor barrier; BTB). What is not well documented is to what degree active efflux retains function at the BTB despite the changes observed in passive permeability. In addition, there have been previous reports documenting both increased and decreased expression of P-gp in lesion vasculature. Herein, we simultaneously administer a passive diffusion marker (14C-AIB) and a tracer subject to P-gp efflux (rhodamine 123) into a murine preclinical model of brain metastases of breast cancer. We observed that the metastatic lesions had similar expression (p>0.05; n=756-1214 vessels evaluated) at the BBB and the BTB. Moreover, tissue distribution of R123 was not significantly (p>0.05) different between normal brain and the metastatic lesion. It is possible that the similar expression of P-gp on the BBB and the BTB contribute to this phenomenon. Additionally we observed P-gp expression at the metastatic cancer cells adjacent to the vasculature which may also contribute to reduced R123 uptake into the lesion. The data suggest that despite the disrupted integrity of the BTB, efflux mechanisms appear to be intact, and may be functionally comparable to the normal BBB. The BTB is a significant hurdle to delivering drugs to brain metastasis