Identification of Potential Antitubulin Agents with Anticancer Assets from a Series of Imidazo[1,2-a]quinoxaline Derivatives: In Silico and In Vitro Approaches.

Computer-aided drug design is a powerful and promising tool for drug design and development, with a reduced cost and time. In the current study, we rationally selected a library of 34 fused imidazo[1,2-a]quinoxaline derivatives and performed virtual screening, molecular docking, and molecular mechanics for a lead identification against tubulin as an anticancer molecule. The computational analysis and pharmacophoric features were represented as 1A2; this was a potential lead against tubulin, with a maximized affinity and binding score at the colchicine-binding site of tubulin. The efficiency of this lead molecule was further identified using an in vitro assay on a tubulin enzyme and the anticancer potential was established using an MTT assay. Compound 1A2 (IC50 = 4.33-6.11 µM against MCF-7, MDA-MB-231, HCT-116, and A549 cell lines) displayed encouraging results similar to the standard drug colchicine in these in vitro studies, which further confirmed the effectiveness of CADD in new drug developments. Thus, we successfully applied the utility of in silico techniques to identify the best plausible leads from the fused azaheterocycles.

Chromenes - A Novel Class of Heterocyclic Compounds: Recent Advancements and Future Directions.

Chromenes are an important class of oxygen-containing heterocyclic compounds with intriguing biological activity, a simple structure with mild adverse effects. Chromenes are abundantly found in nature in the form of alkaloids, tocopherols, flavone, and anthocyanins. The Chromene nucleus is an important moiety for the discovery of new drug candidates. Chromene derivatives have shown various pharmacological activities like antiviral, anticancer, anti-inflammatory, antitumour, antimicrobial, antiproliferative, anticholinesterase, EPR-1 (Effector cell Protease Receptor-1) antagonist and MAO (Mono-Amine Oxidase) inhibitors. In SAR (Structure Activity Relationship) studies with chromene nucleus, it was found that 4-aryl moiety, 3-cyano group, and 2-amino group are essential for the cytotoxic activity. Substitution at the 7th position with electron donating group enhances the pharmacological activity whereas the electron withdrawing group decreases the pharmacological activity. Structural modifications at the chromene ring, middle aliphatic portion, and terminal aromatic ring yielded more potential 5-HT1A (5-Hydroxytryptamine 1A) receptor affinity and antidiabetic activity. Chromenes with cyclic secondary amine and 4-hydroxy phenyl substituents yielded potent antimicrobial compounds. This review summarizes the importance of chromenes in rational drug design and the development of novel molecules with a variety of pharmacological activities.

Improvement in Digestion Resistibility of Mandua Starch (Eleusine coracana) after Cross-Linking with Epichlorohydrin.

Starch, being a polymer of excessive demand for the development of products of pharmaceutical importance, has been tremendously treated in many ways for improving the desired characteristics such as viscosity, paste clarity, digestibility, swelling, syneresis, and so forth. In the present study, alkali-extracted starch of mandua grains (Eleusine coracana; family Poaceae) was treated with epichlorohydrin for cross-linking and the modified starch was assessed for swelling, solubility, water binding capacity, moisture content, and degree of cross-linking. The digestion resistibility of modified starch was analyzed in simulated gastric fluid (pH 1.2), simulated intestinal fluid (pH 6.8), and simulated colonic fluid (pH 7.4). The structural modifications in treated mandua starch were analyzed by Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (XRD), scanning electron microscopy, thermogravimetric analysis, and C13 nuclear magnetic resonance (13C NMR). The results of the study reflected the significant modification in mandua starch after treatment with epichlorohydrin (1.0% w/w sdb, solid dry basis). The degree of cross-linking of treated mandua starch was 85.15%, and the swelling capacity of mandua starch changed from 226.51 ± 2.175 to 103.14 ± 1.998% w/w after cross-linking with epichlorohydrin. A remarkable increment in digestion resistibility was observed in modified mandua starch. The XRD pattern and FTIR spectra revealed the presence of resistant starch after chemical modification. The decomposition pattern of modified mandua starch was also different from extracted mandua starch. All the results reflected the effective modification of mandua starch by epichlorohydrin and the formation of resistant starch to a significant content. The treated mandua starch may have the potential in developing various preparations of food, nutraceuticals, and pharmaceuticals.

Mucoadhesive microspheres of glutaraldehyde crosslinked mucilage of Isabgol husk for sustained release of gliclazide.

Mucoadhesive microspheres have their own significant amongst the various sustained release drug delivery systems. The prolonged residence time of these delivery devices at drug absorption site results in steep concentration gradient and enhanced bioavailability. In this study, the mucilage of Isabgol husk was applied as polymeric backbone to develop gliclazide loaded microspheres by crosslinking with glutaraldehyde. The formulations were studied for surface morphology, swelling behavior, particle size, in vitro release, release kinetics, in vitro mucoadhesion and gamma scintigraphy in rabbits. The release of gliclazide from microspheres was controlled by swelling of crosslinked microspheres followed by diffusion. Gamma scintigraphic images acquired for microspheres retention in gastrointestinal track of rabbits indicated the residence of formulation upto 24 h after oral administration. Gliclazide retained its integrity in polymeric matrix of microspheres as observed by Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffractometry. The sustained release of gliclazide and prolonged retention of microspheres in gastrointestinal track disclosed the rationality of mucoadhesive Isabgol husk microspheres in controlling the hyperglycemia in diabetes.

Mucoadhesivity Characterization of Isabgol Husk Mucilage Microspheres Crosslinked by Glutaraldehyde.

The microspheres of Isabgol husk were prepared by emulsification-crosslinking technique and the gastrointestinal transition behavior of the formulation was studied by gamma scintigraphy. The impact of different process variables such as amount of glutaraldehyde, concentration of Isabgol husk and temperature was studied on surface morphology and mucoadhesion. In vitro mucoadhesive testing of formulations was performed by determination of zeta potential, mucus glycoprotein assay and mucus adsorption isotherms. The effect of feeding on retention of microspheres in the gastrointestinal track (GIT) was studied in albino rabbits by gamma scintigraphy study. The results indicated the formation of microspheres as observed by scanning electron microscopy. The smooth and round surfaces of microspheres were obtained on increasing Isabgol husk and glutaraldehyde amount. The positive zeta potential of all formulations indicated the electrostatic interaction as a mechanism of mucoadhesion between the mucus of GIT membranes and the microspheres surfaces. The influence of electrostatic interaction on mucoadhesion of microspheres was again ascertained when the mucin equilibrium adsorption on preparations indicated well fitness in Langmuir and Freundlich adsorption isotherms. During gamma scintigraphy, the stability of (99m)Tc-sodium pertechnetate was found 98.82% at pH 6.8 and 96.78% at pH 7.2, respectively. It indicated the minimal leaching of bound radionuclide from microspheres during gastrointestinal transition as observed in gamma scintigraphic images of the rabbits. The microspheres retained in GIT even after 24 hrs of oral administration. The results indicated the applicability of Isabgol husk mucilage in the development of mucoadhesive microspheres.