Ankur Vaidya

Recent developments and biological activities of thiazolidinone derivatives: A review

Thiazolidinone is considered as a biologically important active scaffold that possesses almost all types of biological activities. Successful introduction of ralitoline as a potent anti-convulsant, etozoline as a antihypertensive, pioglitazone as a hypoglycemic agent and thiazolidomycin activity against streptomyces species proved potential of thiazolidinone moiety. This diversity in the biological response profile has attracted the attention of many researchers to explore this skeleton to its multiple potential against several activities. This review is complementary to earlier reviews and aims to review the work reported on various biological activities of thiazolidinone derivatives from year 2000 to the beginning of 2011. Data are presented for active compounds, some of which have passed the preclinical testing stage.

1,3,4-Thiadiazole and its Derivatives: A Review on Recent Progress in Biological Activities

The 1,3,4‐thiadiazole nucleus is one of the most important and well‐known heterocyclic nuclei, which is a common and integral feature of a variety of natural products and medicinal agents. Thiadiazole nucleus is present as a core structural component in an array of drug categories such as antimicrobial, anti‐inflammatory, analgesic, antiepileptic, antiviral, antineoplastic, and antitubercular agents. The broad and potent activity of thiadiazole and their derivatives has established them as pharmacologically significant scaffolds. In this study, an attempt has been made with recent research findings on this nucleus, to review the structural modifications on different thiadiazole derivatives for various pharmacological activities.

Metronidazole loaded pectin microspheres for colon targeting

A multiparticulate system having pH-sensitive property and specific enzyme biodegradability for colon-targeted delivery of metronidazole was developed. Pectin microspheres were prepared using emulsion-dehydration technique. These microspheres were coated with Eudragit(R) S-100 using oil-in-oil solvent evaporation method. The SEM was used to characterize the surface of these microspheres and a distinct coating over microspheres could be seen. The in vitro drug release studies exhibited no drug release at gastric pH, however continuous release of drug was observed from the formulation at colonic pH. Further, the release of drug from formulation was found to be higher in the presence of rat caecal contents, indicating the effect of colonic enzymes on the pectin microspheres. The in vivo studies were also performed by assessing the drug concentration in various parts of the GIT at different time intervals which exhibited the potentiality of formulation for colon targeting. Hence, it can be concluded that Eudragit coated pectin microspheres can be used for the colon specific delivery of drug.

Bioconjugation of polymers: a novel platform for targeted drug delivery.

Bioconjugation, a novel technique is usually exploited to improve the biopharmaceutical aspects of a bioactive as well as afford its spatial and temporal distribution. The strategy enlightens newer vistas for delivery of drugs, peptides, enzymes, and oligonucleotides. Site specific delivery may be obtained by tailoring the conjugates as an inactive prodrug and designing polymer drug linkages susceptible to cleavage by specific enzymes or pH. These prodrugs substantially change the mechanisms of cellular entry, pharmacokinetic disposition and ultimately target the drug. The conjugate vehicles are being exploited for targeting pharmacological agents to visceral tissues viz brain, colon etc. These biomaterials are bringing into play, novel drug delivery systems for selectively and specifically ferrying drugs to the desired organ. Noteworthy contributions reported with bioconjugated nanoparticles for biosensing and bioimaging incorporate cell staining, DNA detection, separation and recombination relevance in DNA protection. Only recently, these tailor-made polymers have also gained impetuous for enzyme therapy, gene therapy, insulin therapy, cancer therapy and management of AIDS with the interception of minimal side effects. The present review exhaustively provides an insight to the polymer bioconjugates and their implications for targeted delivery. The article also discusses the therapeutic aspects of these conjugates and that these may serve as fascinating tools for drug delivery.

Metabotropic Glutamate Receptors: A Review on Prospectives and Therapeutic Aspects

The metabotropic glutamate (mGluRs) receptors are a distinct class of G-protein-coupled receptors that act through activation of phospholipase C and/or inhibition of adenylate cyclase. They encompass seven-transmembrane domain proteins, comprehensively expressed in neuronal and glial cells within the brain, spinal cord and periphery and are involved in controlling pathophysiology of a number of diseases. These receptors may be sorted into three groups based on similarity of amino acid sequence, pharmacology and the transducer pathways they couple. The agonists and antagonists act at the N-terminal glutamate binding site and present a pharmacological strategy to modulate pathogenesis. A number of these compounds are positive or negative allosteric modulators that bind within the receptor transmembrane heptahelical domains. This imparts improved subtype selectivity, improved bioavailability and better drug like properties (e.g. CNS penetration). The mGluRs are presently the focal point of sizeable attention because of their potential as drug targets for the treatment of neurological and psychiatric disorders of the brain including Schizophrenia, Alzheimers disease, Parkinsons disease, addiction, anxiety, depression, epilepsy and pain. The present review focuses on signal transduction mechanisms implicated to control and functionally upregulate the glutamatergic transmission system. The article also hallmarks agonists and antagonists for mGluRs as pivotal agents to ameliorate an array of neurological and psychiatric disorders.

Synthesis and Biological Activities of Oxadiazole Derivatives: A Review.

Recently, there has been wide interest in compounds containing the oxadiazole scaffold because of their unique chemical structure and their broad spectrum of biological properties. This review provides readers with an overview of the main synthetic methodologies for oxadiazoles and of their broad spectrum of pharmacological activities such as, anti-microbial, anti-fungal activity, antiviral, anti-tubercular, anti-inflammatory, anti-convulsant, anti-angiogenic, anti-proliferative, analgesic, anti-oedema and in alzheimer activity, which were reported over the past years.

Predicting anti-cancer activity of quinoline derivatives: CoMFA and CoMSIA approach

The 3D quantitative structure-activity relationships of 31 quinoline nuclei containing compounds and their biological activity have been investigated to establish various models. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies resulted in reliable and significant computational models. The obtained CoMFA model showed high predictive ability with q2 = 0.592, r2 = 0.966 and standard error of estimation (SEE) = 0.167, explaining majority of the variance in the data with two principal components. Predictions obtained with CoMSIA steric, electrostatic, hydrophobic, hydrogen-bond acceptor and donor fields (q2 = 0.533, r2 = 0.985) showed high prediction ability with minimum SEE (0.111) and four principal components. The information obtained from the CoMFA and CoMSIA contour maps can be utilized for the design and development of topoisomerase-II inhibitors for synthesis.

Molecular therapy using siRNA: Recent trends and advances of multi target inhibition of cancer growth

RNA interference (RNAi) therapy, harnessed to produce a new class of drugs for treatment, has drawn attention and seen steady progress over the years. Molecular therapy using biological macromolecules small interfering RNA (siRNA) for gene silencing has received significant attention to target cancer-related genes. Basically, siRNA molecules bind to messenger RNAs (mRNA) by complementary base pairing, to induce degradation of the mRNA and/or block protein synthesis. Numerous genes and gene related proteins have been reported till date to target in siRNA based cancer therapy. Furthermore, a combination of siRNA with traditional anticancer drugs produces synergistic anticancer effect, or overcomes drug resistance, enhances targeting abilities and minimizes side-effects. Current review highlights various functional properties of genes that can be selectively knocked down by siRNAs. In addition, we have also discussed the interaction of siRNA-mediated gene-silencing with chemotherapeutic agents in nanoformulation which constitutes a valuable and safe approach for cancer treatment.

Anticancer Potential of Thiazole Derivatives: A Retrospective Review

This review brings forth the potential of thiazole derivatives for their anticancer activities. The emphasis is placed on the structural diversity of thiazole derivatives, responsible for their specific anticancer activity. Multiple classes of thiazole derivatives such as Schiff base, mono-, di-, tri-, and heterocyclic substituents that possess anticancer activity have been exemplified. Molecular modelling of compounds that predicts enhanced anticancer activity of the modified structures has also been elaborated in the review. Significant advancements in synthetic chemistry related to cytotoxicity can now better position the drug discovery team to undertake thiazoles as valuable leads. The beneficial thiazole derivatives possessing anticancer activity will reignite the interest of medicinal chemists in thiazole and their derivatives.

Computational analysis of quinoline derivatives as potent topoisomerase-II inhibitors

Quantitative structure–activity relationship (QSAR) is an attempt to correlate structural or property descriptors of compounds quantitatively with biological activities. QSARs currently are being applied in many disciplines, with many pertaining to drug design and environmental risk assessment. The 3D QSARs between the structures of 29 quinoline compounds and their topoisomerase-II inhibitor activity have been developed using the comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and stepwise k nearest neighbor molecular field analysis [(SW) kNN MFA] method, and 3D QSAR models with the considerable prediction ability are obtained. The CoMFA, CoMSIA, and [(SW) kNN MFA] studies resulted in reliable and significant computational models. These models are more significant guide to trace the important chemical features with respect to the design of new potent compounds. The information obtained from the CoMFA, CoMSIA, and [(SW) kNN MFA] contour maps can be utilized for the design and development of new, more potent topoisomerase-II inhibitor.