Synthesis, Spectral Characterization and Anticonvulsant Studies of the Novel Triazolothiadiazoles Bearing Benzoxazole Moiety

In this study, new fused triazolo-thiadiazoles (4a-o) were synthesized viamethyl 2-[bromo(phenyl)methyl]-1,3-benzoxazole-5-carboxylate. The structure of novel derivatives was recognized on the basis of spectral data results and screened their anticonvulsant action by means of maximal electroshock seizure (MES) and subcutaneous pentylenetetrazol (scPTZ) procedures. Minimal motor studies were completed by a rotarod method. Compounds 4e, 4g, 4j, 4l, 4m and 4n showing better anticonvulsant action corresponding to hydrophobicity. Other molecules remained fewer lipophilic and have less effectiveness. Most of the compounds positively tolerable the rotarod test deprived of motor deficiency. In conclusion, the prepared derivatives with distal aryl moiety exhibited higher lipophilic character and lead to improved pharmacological achievement, which can be a forthcoming promise.

Correction to: The acrid raphides in tuberous root of Pinellia ternata have lipophilic character and are specifically denatured by ginger extract

A correction to this paper has been published: https://doi.org/10.1007/s11418-021-01501-5

Easy-To-Access Quinolone Derivatives Exhibiting Antibacterial and Anti-Parasitic Activities

The cell wall of Mycobacterium tuberculosis (Mtb) has a unique structural organisation, comprising a high lipid content mixed with polysaccharides. This makes cell wall a formidable barrier impermeable to hydrophilic agents. In addition, during host infection, Mtb resides in macrophages within avascular necrotic granulomas and cavities, which shield the bacterium from the action of most antibiotics. To overcome these protective barriers, a new class of anti-TB agents exhibiting lipophilic character have been recommended by various reports in literature. Herein, a series of lipophilic heterocyclic quinolone compounds was synthesised and evaluated in vitro against pMSp12::GFP strain of Mtb, two protozoan parasites (Plasmodium falciparum and Trypanosoma brucei brucei) and against ESKAPE pathogens. The resultant compounds exhibited varied anti-Mtb activity with MIC90 values in the range of 0.24–31 µM. Cross-screening against P. falciparum and T.b. brucei, identified several compounds with antiprotozoal activities in the range of 0.4–20 µM. Compounds were generally inactive against ESKAPE pathogens, with only compounds 8c, 8g and 13 exhibiting moderate to poor activity against S. aureus and A. baumannii.

Lipophilicity Determination of Quaternary (Fluoro)Quinolones by Chromatographic and Theoretical Approaches

Lipophilicity is a vital physicochemical parameter of a molecule, which affects several biological processes such as absorption, tissue distribution, and pharmacokinetic properties. In this study, evaluation of lipophilicities of a series of novel fluoroquinolone-Safirinium dye hybrids using chromatographic and computational methods is presented. Fluoroquinolone-Safirinium dye hybrids have been synthesized as new dual-acting hydrophilic antibacterial agents. Reversed phase thin-layer chromatography and micellar electrokinetic chromatography experiments were carried out. Furthermore, logP values of the target structures were predicted by means of different software platforms and algorithms. In order to assess similarities and dissimilarities of the obtained lipophilicity indexes, cluster analysis and sum of ranking differences were performed. The significant differences of calculated logP values (α = 0.05, p < 0.001) indicated that an experimental approach is necessary for lipophilicity prediction of this class of antibiotics. Chromatographic data indicated that the newly synthesized hybrid (fluoro)quinolone-based quaternary ammonium derivatives show less lipophilic character than the parent (fluoro)quinolones. Additionally, the chromatographically obtained lipophilicity indexes were evaluated for possible application in quantitative retention–activity relationships. The established lipophilicity models have the potential to predict antimicrobial activities of a series of quaternary (fluoro)quinolones against Bacillus subtilis, Escherichia coli, and Proteus vulgaris.

In vivoprogramming of tumor mitochondria-specific doxorubicin delivery by a cationic glycolipid polymer for enhanced antitumor activity

C-P-CSOSA/DOX exhibited effective mitochondria-targeted capabilityin vitroandin vivo, based on a skeletal polymer with cationic and lipophilic character.

Lipophilic halogen-free ionic liquid with antibacterial and anti-biofilm activities against Pseudomonas aeruginosa

A halogen-free ionic liquid (IL) designed with long alkyl chain anion is reported. 1-methylimidazolium stearate (MIM stearate) synthesized through Bronsted acid-base reaction has shown improved lipophilic character and is able to penetrate bacterial cell walls. Antimicrobial activities against Gram-negative bacteria, Escherichia coli, and Pseudomonas aeruginosa were observed. Anti-biofilm assays showed effectivity against the biofilm of Pseudomonas aeruginosa. At 50 µg/mL the %biofilm inhibition of MIM stearate towards P. aeruginosa biofilm formation is comparable to the Bromofuran positive control. Brine shrimp lethality assay showed weak toxicity indicating the IL to be safe and benign. The synthesized MIM stearate showed good promise as an antimicrobial and anti-biofilm agent.

Anticancer, antimicrobial and antioxidant potential of sterically tuned bis-N-heterocyclic salts

The current study was conducted to evaluate the antimicrobial, antioxidant, antileishmanial and cytotoxic potential of designed derivatives of 1,1′-(1,3-phenylenebis(methylene))bis(3-alkyl/aryl-1H-benzimidazol-3-ium) salts. The antibacterial potential of the test compounds was investigated againstStaphylococcus aureus, Pseudomonas aeruginosaand two methicillin-resistantS. aureus(MRSA) strains (MRSA10, MRSA11), where compound6showed the best results. For brine shrimp lethality bioassay (BSLB), compound6again showed up to 100% mortality at 200 μg/mL and 56.7% mortality at 6.25 μg/mL. Antileishmanial assay was performed againstLeishmania tropicaat 20 μg/mL dosage, where6showed the most promising activity with 16.26% survival (83.74% mortality; IC50=14.63 μg/mL). The anticancer potential of the selected benzimidazole derivatives was evaluated against two selected cell lines (human colorectal cancer, HCT-116 and breast adenocarcinoma, MCF-7) using sulforhodamine B (SRB) assay. Compound6was found to be the most effective cytotoxic compound with 75% inhibition of HCT-116 proliferation at 1 mg/mL concentration. Succinctly,6exhibited impressive pharmacological potential that might be attributed to its higher lipophilic character owing to the longer N-substituted alkyl chains when compared to the other test compounds.

A comprehensive review on Liposomes: a novel drug delivery system

Liposome was derived from two Greek words “Lipos meaning fat and Soma meaning body”. Liposome were spherical shaped vesicles consist of phospholipids and cholesterol. Due to their size hydrophobic and lipophilic character they are very promising system for drug delivery. This novel drug delivery system aims to target the drug directly to the site of action. Liposomes are very biocompatible and stable and have unique property to entrap both hydrophilic drug and lipophilic drug (amphiphatic nature) to its compartment and lead to controlled release effect. They are of 0.05- 5.0 micrometer in diameter. Liposomes are used for the treatment of various diseases like tumors or cancer. This article provides an overview of Liposomal Drug Delivery System and various aspects related to liposome that can be studied. Keywords: Liposomes, novel delivery, amphiphatic, controlled release.

SYNTHESIS, SPECTRAL, AND PHARMACOLOGICAL EVALUATION OF 3 AND 5 SUBSTITUTED 2,4-THIAZOLIDINEDIONE DERIVATIVES

Background: 2,4-Thiazolidinedione derivatives was launched as antidiabetics in 90’s. Later the derivatives of 2,4-thiazolidinedione were banned due to hepatotoxicity. To the date, much research has been directed toward the synthesis and novel uses of 2,4-thiazolidinedione compounds.Aim: The aim of the present study is to synthesize a set of 3,5-disudstituted-2,4-thiazolidinediones as antimicrobial. These compounds were evaluated for their antimicrobial activity.Method: First, the 2,4-thiazolidinedione was substituted at the position of 3 using sodium hydroxide and ethanol and then substituted at the position of 5 in the presence of piperdine by the Knoevenagel condensation method. The structures of the compounds were established on the basis of infrared and nuclear magnetic resonance spectral studies.Result: 3,5-disubstituted-5-benzylidine-2,4-thiazolidinediones derivative was synthesized using benzyl halides and aromatic aldehydes. The results obtained showed that TZ-1 exhibited good activity against Bacillus subtilis while no activity against Escherichia coli.Conclusion: Attachment of more heterocyclic rings containing Nitrogen on the 3rd position of 2,4-thiazolidinedione can enhance the antimicrobial activity. Addition of more lipophilic agents may increase the bioavailability and efficacy of the drug. Long alkyl chains on the benzylidene ring can also increase the lipophilic character, and further attachment of these kind of agents on benzylidene chain may produce safe and effective compounds in future.