Uttam A. More

Polysaccharide-based micro/nanohydrogels for delivering macromolecular therapeutics.

Increased interest in developing novel micro/nanohydrogel based formulations for delivering macromolecular therapeutics has led to multiple choices of biodegradable and biocompatible natural polymers. This interest is largely due to the availability of large number of highly pure recombinant proteins and peptides with tunable properties as well as RNA interference technology that are used in treating some of the deadly diseases that were difficult to be treated by the conventional approaches. The majority of marketed drugs that are now available are in the form of injectables that pose limited patient compliance and convenience. On the other hand, micro/nanotechnology based macromolecular delivery formulations offer many alternative routes of administration and advantages with improved patient compliance and efficient or targeted delivery of intracellular therapeutics to the site of action. This review outlines and critically evaluates the research findings on micro and nano-carrier polymeric hydrogels for the delivery of macromolecular therapeutics.

Controlled release of therapeutics using interpenetrating polymeric networks

Introduction: The ever-increasing developments in pharmaceutical formulations have led to the widespread use of biodegradable polymers in various forms and configurations. In particular, interpenetrating network (IPN) and semi-IPN polymer structures that are capable of releasing drugs in a controlled manner have gained much wider importance in recent years. Areas covered: Recently, IPNs and semi-IPNs have emerged as innovative materials of choice in controlled release (CR) of drugs as the release from these systems depends on pH of the media and temperature in addition to the nature of the system. These networks can be prepared as smart hydrogels following chemical or physical crosslinking methods to show remarkable drug release patterns compared to single polymer systems. Expert opinion: A large number of IPNs and semi-IPNs have been reported in the literature. The present review is focused on the preparation methods and their CR properties with reference to anticancer, anti-asthmatic, antibiotic, anti-inflammatory, anti-tuberculosis and antihypertensive drugs, as majority of these drugs have been reported to be the ideal choices for using IPNs and semi-IPNs.

Multi-spectroscopic investigation of the binding interaction of fosfomycin with bovine serum albumin☆

The interaction between fosfomycin (FOS) and bovine serum albumin (BSA) has been investigated effectively by multi-spectroscopic techniques under physiological pH 7.4. FOS quenched the intrinsic fluorescence of BSA via static quenching. The number of binding sites n and observed binding constant KA were measured by the fluorescence quenching method. The thermodynamic parameters ΔG0, ΔH0 and ΔS0 were calculated at different temperatures according to the van’t Hoff equation. The site of binding of FOS in the protein was proposed to be Sudlow’s site I based on displacement experiments using site markers viz. warfarin, ibuprofen and digitoxin. The distance r between the donor (BSA) and acceptor (FOS) molecules was obtained according to the Förster theory. The effect of FOS on the conformation of BSA was analyzed using synchronous fluorescence spectra (SFS), circular dichroism (CD) and 3D fluorescence spectra. A molecular modeling study further confirmed the binding mode obtained by the experimental studies.

Guar gum as platform for the oral controlled release of therapeutics

Introduction: The past decade of research has witnessed a huge advancement in research efforts on guar gum (GG)-based polymers as controlled release (CR) formulations for the delivery of therapeutics. Areas covered: The unique structure and beneficial properties of GG makes it an attractive biomaterial in CR applications. Current status on GG-based polymers has been addressed as a CR formulation in the form of microspheres, nanoparticles, hydrogels and matrix tablets for the delivery of various types of therapeutics having a wide range of physicochemical properties. Majority of literature on GG as a platform technology has dealt with oral route of drug administration as it is the most convenient, patient-compliant and preferred approach. Recent reports on GG-based polymers are summarized and critically discussed to narrate their usefulness as oral delivery systems. Expert opinion: The research on GG-based formulations has been focused on optimization of the therapy by designing CR dosage forms with a minimum number of excipients. In this context, GG-based polymers are quite attractive. The present review summarizes published reports on these systems and offers expert opinion relevant to oral delivery of therapeutics.

Enoyl ACP reductase as effective target for the synthesized novel antitubercular drugs: a-state-of-the-art.

The emergence of drug resistant strains of important human pathogens has created an urgent necessity to find new targets and novel antitubercular agents. According to the literature survey, we noticed that enoyl ACP reductase is one of the most promising targets. This enzyme is the most important catalyst for the FAS II synthesis of mycolic acid, which is the most essential component of the mycobacterial cell wall. This review summarizes the progress made in the design of enoyl ACP reductase inhibitors and the role played by 3D-structure of the enzyme in drug design process.

In vitro studies on the interaction between human serum albumin and fosfomycin disodium salt, an antibiotic drug by multi-spectroscopic and molecular docking methods

The interaction between the human serum albumin (HSA) and drug, fosfomycin disodium salt (FOS) has been studied by different spectroscopic techniques. The experimental results showed a static quenching mechanism in the interaction of FOS with HSA. The number of binding sites, n and observed binding constant Ka were measured by fluorescence quenching method. The thermodynamic parameters ΔG°, ΔH° and ΔS° were calculated according to van’t Hoff equation. The calculated distance r between FOS and the protein is evaluated according to the theory of Förster energy transfer. A change in the secondary structure of the protein was evident from the circular dichroism measurements, synchronous fluorescence and three-dimensional fluorescence spectra.

Graph Theoretical Analysis, Insilico Modeling, Design, and Synthesis of Compounds Containing Benzimidazole Skeleton as Anti-depressant Agents

In this study, drug target was identified using KEGG database and network analysis through Cytoscape software. Designed series of novel benzimidazoles were taken along with reference standard Flibanserin for insilico modeling. The novel 4‐(1H‐benzo[d]imidazol‐2‐yl)‐N‐(substituted phenyl)‐4‐oxobutanamide (3a–j) analogs were synthesized and evaluated for their antidepressant activity. Reaction of 4‐(1H‐benzo[d]imidazol‐2‐yl)‐4‐oxobutanoic acid (1) with 4‐(1H‐benzo [d] imidazol‐2‐yl)‐4‐oxobutanoyl chloride (2) furnished novel 4‐(1H‐benzo [d] imidazol‐2‐yl)‐N‐(substituted phenyl)‐4‐oxobutanamide (3a–j). All the newly synthesized compounds were characterized by IR, 1H‐NMR, and mass spectral analysis. The antidepressant activities of synthesized derivatives were compared with standard drug clomipramine at a dose level of 20 mg/kg. Among the derivatives tested, most of the compounds were found to have potent activity against depression. The high level of activity was shown by the compounds 3d, 3e, 3i, and it significantly reduced the duration of immobility time at the dose level of 50 mg/kg.

Design and development of pyrrole carbaldehyde: an effective pharmacophore for enoyl-ACP reductase

Enoyl-ACP reductase is the key enzyme involved in FAS-II synthesis of mycolic acid in bacterial cell wall and is a promising target for discovering new chemical entity. The designed pharmacophores are the possible better tools to combat mutation in enoyl-ACP enzyme, which leads to a decrease in volume of triclosan binding site. Compound 3a showed H-bonding interactions similar to that of triclosan with enoyl-ACP enzyme and with a better docking score (C score 8.81), while the compound 3f showed additional interaction with MET98.H amino acid residue. The 3D-QSAR computations also support the docking study to develop novel pyrrole-based derivatives.Graphical abstractMolecular docking 3D-QSAR studies and synthesis of active analogs of pyrrole carbaldehyde as better receptor fit pharmacophore for enoyl-ACP reductase along with in vitro antitubercular activity.

Pyrrolyl thiadiazoles as Mycobacterium tuberculosis inhibitors and their in silico analyses

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Research and Reports in Medicinal Chemistry 2015:5 1–20 Research and Reports in Medicinal Chemistry Dovepress

3D-QSAR studies of quinoline Schiff bases as enoyl acyl carrier protein reductase inhibitors

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Research and Reports in Medicinal Chemistry 2014:4 59–75 Research and Reports in Medicinal Chemistry Dovepress