Synthesis and antitubercular evaluation of 2-iminothiazolidine-4-ones

In the present manuscript, we report synthesis of new 3 and 5 substituted 2-imino thiazolidine-4-ones by three step synthetic protocols from 3-trifluormethyl aniline or 2-amino heterocycle. The compounds were evaluated for in vitro activities against Mycobacterium tuberculosis (MTB) in presence and absence of efflux pump inhibitor, cytotoxicity against RAW 264.7 cells. Among the thirty six compounds, 2-imino-3-(5-nitrothiazol-2-yl)-5-(3,4,5-trimethoxybenzylidene)thiazolidin-4-one (5g) was found to be the most active compound in vitro with MICs of 3.31 µM against log-phase culture of MTB and also non-toxic up to 100 µM. Compound 5g showed minimum inhibitory concentration (MIC) of 0.82 µM against MTB in presence of efflux pump inhibitor verapamil

Effect of Solution Properties and Operating Parameters on Needleless Electrospinning of Poly (Ethylene Oxide) Nanofibers Loaded with Bovine Serum Albumin

Background: This paper presents the effect of solution properties and operating parameters of polyethylene oxide (PEO) based nanofiber using a wire electrode-based needleless electrospinning. Methods: The feed solution was prepared using a PEO dissolved in water or a water-ethanol mixture. The PEO solution is blended with Bovine Serum Albumin protein (BSA) as a model drug to study the effect of the electrospinning process on the stability of the loaded protein. The polymer solution properties such as viscosity, surface tension, and conductivity were controlled by adjusting the solvent and salt content. The morphology and fiber size distribution of the nanofiber was analyzed using scanning electron microscopy. Results: The results show that the issue of a beaded nanofiber can be eliminated either by increasing the solution viscosity or by the addition of salt and ethanol to the PEO-water system. The addition of salt and solvent produced a high frequency of smaller fiber diameter ranging from 100 to 150 nm. The encapsulation of BSA in PEO nanofiber was characterized by three different spectroscopy techniques (i.e. circular dichroism, Fourier transform infrared, and fluorescence) and the results showed the BSA is well encapsulated in the PEO matrix with no changes in the protein structure. Conclusion: This work may serve as a useful guide for a drug delivery industry to process a nanofiber at a large and continuous scale with a blend of drugs in nanofiber using a wire electrode electrospinning

Investigating structure–activity relationship and mechanism of action of antitubercular 1-(4-chlorophenyl)-4-(4-hydroxy-3-methoxy-5-nitrobenzylidene) pyrazolidine-3,5-dione [CD59]

Background and objectives: The objective of this study is to synthesize and evaluate 1-(4-chlorophenyl)-4-(4-hydroxy-3-methoxy-5-nitrobenzylidene) pyrazolidine-3,5-dione (CD59) analogues to establish structure–activity relationship and mechanism of action. Methods: Thirty analogues of reported antitubercular CD59 were prepared by two-step synthetic protocols and characterized. The compounds were evaluated for in vitro activities against Mycobacterium tuberculosis (MTB), cytotoxicity against RAW 264.7 cells. The molecules were also evaluated for three mycobacterial enzymes to study the mechanism of action. Results: Among the compounds, 4-(2-bromobenzylidene)-1-(4-chlorophenyl)pyrazolidine-3,5-dione (4k) was found to be the most active compound in vitro with MICs of 4.13 μM against log-phase culture of MTB and also non-toxic up to 50 μM. Conclusions: Amongst all, the compounds 4g, 3i and 3n were most active against the enzymes MTB Pantothenate synthetase, lysine amino transferase and Alanine dehydrogenase, respectively. Further screening of these molecules was required in the in vitro dormant MTB models

A Low-Molecular-Weight Gelator Composed of Pyrene and Fluorene Moieties for Effective Charge Transfer in Supramolecular Ambidextrous Gel

Charge-transfer (CT) gel materials obtained from low-molecular-weight (LMW) compounds through a supramolecular self-assembly approach have received fascinating attention by many researchers because of their interesting material property and potential applications. However, most of the CT gel materials constructed were of organogels while the construction of CT gels in the form of a hydrogel is a challenge because of the solubility issue in water, which considerably limits the use of CT hydrogels. Herein, for the first time, we report a new LMW gelator [<i>N</i>^α-(fluorenylmethoxycarbonyl)-<i>N</i>^ε-(δ-butyric-1-pyrenyl)-l-lysine, (FmKPy)], composed of two functional moieties such as fluorenylmethoxycarbonyl and pyrene, which not only parade both hydro and organo (ambidextrous) supramolecular gel formation but also exhibit CT ambidextrous gels when mixed with an electron acceptor such as 2,4,7-trinitro-9-fluorenone (TNF). This finding is significant as the established CT organogelator in the literature did not form an organogel in the absence of an electron acceptor or lose their gelation property upon the addition of the acceptor. CT between pyrene and TNF was confirmed by the color change as well as the appearance of the CT band in the visible region of the absorption spectrum. CT between FmKPy and TNF was supported by the solvent dilution method using tetrahydrofuran as the gel breaker and pyrene fluorescence quenching in the case compound containing pyrene and TNF. The morphology of FmKPy ambidextrous gels indicates the fibrous nature while the self-assembled structure is primarily stabilized by π–π stacking among fluorenyl and pyrenyl moieties and hydrogen bonding between amide groups. The FmKPy–TNF CT ambidextrous gel retains the fibrous nature; however, the size of the fibers changed. In FmKPy–TNF CT gels, TNF is intercalated between pyrene moieties in the self-assembled structure as confirmed by fluorescence quenching and powder X-ray diffraction. The FmKPy ambidextrous gel exhibits significant properties such as low minimum gelation concentration (MGC), thixotropic nature, pH stimuli response, and high thermal stability. Upon the addition of TNF, the FmKPy–TNF CT ambidextrous gel maintains all these properties except MGC which increased for FmKPy–TNF. Because pyrene-based LMW organogels have been developed widely for many applications while their hydrogels were limited, the current finding of the pyrene-based ambidextrous fluorescent gel with the CT property provides a wide opportunity to use FmKPy as a soft material maker and also for potential applications in fields like surface coating, three-dimensional printing, and so forth