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.     

Recent advances in the synthetic and medicinal perspective of quinolones: A review

In the modern scenario, the quinolone scaffold has emerged as a very potent motif considering its clinical significance. Quinolones possess wide range of pharmacological activities such as anticancer, antibacterial, antifungal, antiprotozoal, antiviral, anti-inflammatory, carbonic anhydrase inhibitory and diuretic activity etc. The versatile synthetic approaches have been successfully applied and several of the resulted synthesized compounds exhibit fascinating biological activities in numerous fields. This has prompted to discover quinolone-based analogues among the researchers due to its great diversity in biological activities. In the past few years, various new, efficient and convenient synthetic approaches (including green chemistry and microwave-assisted synthesis) have been designed and developed to synthesize diverse quinolone-based scaffolds which represent a growing area of interest in academic and industry as well as to explore their biological activities. In this review, an attempt has been made by the authors to summarize (1) One of the most comprehensive listings of quinolone-based drugs or agents in the market or under various stages of clinical development; (2) Recent advances in the synthetic strategies for quinolone derivatives as well as their biological implications including insight of mechanistic studies. (3) Further, the biological data is correlated with structure-activity relationship studies to provide an insight into the rational design of more active agents.     

An exhaustive compilation on chemistry of triazolopyrimidine: A journey through decades

The triazolopyrimidine scaffold represents one of the privileged structure in chemistry, and there has been an increase in number of studies utilizing this scaffold and its derivatives. Optimization of synthetic protocols such as aza-Wittig reaction, [3 + 2] cycloaddition reaction along with previous methods including condensation with 1,3-dicarbonyl substrates and oxidation of aminopyrimidine Schiff bases have been performed to obtain desired triazolopyrimidines. The triazolopyrimidine ring has been extensively used as a template in medicinal chemistry for its diverse pharmacological properties. Several medicinally active molecules possessing triazolopyrimidine scaffold, either fused or coupled with other heterocycles, have been reported in the literature, highlighting the significance of this nucleus. Interestingly, the unique triazolopyrimidine scaffold also exhibits an impressive potential as a ligand for the synthesis of several metal complexes with significant biological potential. Literature provides enough evidence of exhaustive exploration of this scaffold as a ligand for the chelates of platinum, ruthenium and other metals. This review aims to be a comprehensive and general summary of the different triazolopyrimidine syntheses, their use as ligands for the synthesis and development of metal complexes as medicinal agents and their main biological activities.     

Thieno[2,3-d]pyrimidine as a promising scaffold in medicinal chemistry: Recent advances

Thienopyrimidine scaffold is a fused heterocyclic ring system that structurally can be considered as adenine, the purine base that is found in both DNA and RNA-bioisosteres. Thienopyrimidines exist in three distinct isomeric forms. The current review discusses thieno[2,3-d]pyrimidine as a one of the opulent heterocycles in drug discovery. Its broad range of medical applications such as anticancer, anti-inflammatory, anti-microbial, and CNS protective agents has inspired us to study its structure-activity relationship (SAR), along with its relevant synthetic strategies. The present review briefly summarizes synthetic approaches for the preparation of thieno[2,3-d]pyrimidine derivatives. In addition, the promising biological activities of this scaffold are also illustrated with explanatory diagrams for their SAR studies.     

Synthesis and biological evaluation of a series of thieno-expanded tricyclic purine 2'-deoxy nucleoside analogues

Introducing structural diversity into the nucleoside scaffold for use as potential chemotherapeutics has long been considered an important approach to drug design. In that regard, we have designed and synthesized a number of innovative 2'-deoxy expanded nucleosides where a heteroaromatic thiophene spacer ring has been inserted in between the imidazole and pyrimidine ring systems of the natural purine scaffold. The synthetic efforts towards realizing the expanded 2'-deoxy-guanosine and -adenosine tricyclic analogues as well as the preliminary biological results are presented herein.     

Evaluation of biological protein-based collagen scaffolds in cartilage and musculoskeletal tissue engineering--a systematic review of the literature

The term tissue engineering is the technology that combines cells, engineering and biological/synthetic material in order to repair, replace or regenerate biological tissues such as bone, muscle, tendons and cartilage. The major human applications of tissue engineering are: skin, bone, cartilage, corneas, blood vessels, left mainstem bronchus and urinary structures. In this systematic review several criteria were identified as the most desirable characteristics of an ideal scaffold. These state that an ideal scaffolds needs to be biodegradable, possess mechanical strength, be highly porous, biocompatible, non-cytotoxic, non antigentic, stuitable for cell attachment, proliferation and differentiation, flexible and elastic, three dimensional, osteoconductive and support the transport of nutrients and metabolic waste. Subsequently, studies reporting on the various advantages and disadvantages of using collagen based scaffolds in musculoskeletal and cartilage tissue engineering were identified. The purpose of this review is to 1) provide a list of ideal characteristics of a scaffold as identified in the literature 2) identify different types of biological protein-based collagen scaffolds used in musculoskeletal and cartilage tissue engineering 3) assess how many of the criteria each scaffold type meets 4) weigh different scaffolds against each other according to their relative properties and shortcomings. The rationale behind this approach is that the ideal scaffold material has not yet been identified. Hence, this review will define how many of the identified ideal characteristics are fulfilled by natural collagen-based scaffolds and address the shortcomings of its use as found in the literature.     

Proteolytic clipping of histone tails: the emerging role of histone proteases in regulation of various biological processes

Chromatin is a dynamic DNA scaffold structure that responds to a variety of external and internal stimuli to regulate the fundamental biological processes. Majority of the cases chromatin dynamicity is exhibited through chemical modifications and physical changes between DNA and histones. These modifications are reversible and complex signaling pathways involving chromatin-modifying enzymes regulate the fluidity of chromatin. Fluidity of chromatin can also be impacted through irreversible change, proteolytic processing of histones which is a poorly understood phenomenon. In recent studies, histone proteolysis has been implicated as a regulatory process involved in the permanent removal of epigenetic marks from histones. Activities responsible for clipping of histone tails and their significance in various biological processes have been observed in several organisms. Here, we have reviewed the properties of some of the known histone proteases, analyzed their significance in biological processes and have provided future directions.     

Structure-activity relationship of the 7-hydroxy benzimidazole analogs as glycogen synthase kinase 3β inhibitor

Design, synthesis and the GSK3β inhibitory activities of the 7-hydroxy benzimidazole analogs are described. The solid-phase synthetic route was also developed for preparation of the analogs consisting of the novel ATP competitive scaffold. In addition, the structure-activity relationship of the 7-hydroxy benzimidazole analogs and their biological activities are reported.     

Tethered thiazolidinone dimers as inhibitors of the bacterial type III secretion system

Disruption of protein–protein interactions by small molecules is achievable but presents significant hurdles for effective compound design. In earlier work we identified a series of thiazolidinone inhibitors of the bacterial type III secretion system (T3SS) and demonstrated that this scaffold had the potential to be expanded into molecules with broad-spectrum anti-Gram negative activity. We now report on one series of thiazolidinone analogs in which the heterocycle is presented as a dimer at the termini of a series of linkers. Many of these dimers inhibited the T3SS-dependent secretion of a virulence protein at concentrations lower than that of the original monomeric compound identified in our screen.     

Recent Updates in Curcumin Pyrazole and Isoxazole Derivatives: Synthesis and Biological Application

Curcumin is an admired, plant‐derived compound that has been extensively investigated for diverse range of biological activities, but the use of this polyphenol is limited due to its instability. Chemical modifications in curcumin are reported to seize this limitation; such efforts are intensively performed to discover molecules with similar but improved stability and better properties. Focal points of these reviews are synthesis of stable pyrazole and isoxazole analogs of curcumin and application in various biological systems. This review aims to emphasize the latest evidence of curcumin pyrazole analogs as a privileged scaffold in medicinal chemistry. Manifold features of curcumin pyrazole analogs will be summarized herein, including the synthesis of novel curcumin pyrazole analogs and the evaluation of their biological properties. This review is expected to be a complete, trustworthy and critical review of the curcumin pyrazole analogs template to the medicinal chemistry community.     

Lung tissue engineering: An update

Pulmonary disease is a worldwide public health problem that reduces the life quality and increases the need for hospital admissions as well as the risk of premature death. A common problem is the significant shortage of lungs for transplantation as well as patients must also take immunosuppressive drugs for the rest of their lives to keep the immune system from attacking transplanted organs. Recently, a new strategy has been proposed in the cellular engineering of lung tissue as decellularization approaches. The main components for the lung tissue engineering are: (1) A suitable biological or synthetic three-dimensional (3D) scaffold, (2) source of stem cells or cells, (3) growth factors required to drive cell differentiation and proliferation, and (4) bioreactor, a system that supports a 3D composite biologically active. Although a number of synthetic as well biological 3D scaffold suggested for lung tissue engineering, the current favorite scaffold is decellularized extracellular matrix scaffold. There are a large number of commercial and academic made bioreactors, the favor has been, the one easy to sterilize, physiologically stimuli and support active cell growth as well as clinically translational. The challenges would be to develop a functional lung will depend on the endothelialized microvascular network and alveolar–capillary surface area to exchange gas. A critical review of the each components of lung tissue engineering is presented, following an appraisal of the literature in the last 5 years. This is a multibillion dollar industry and consider unmet clinical need.     

Medicinal attributes of 1,2,3-triazoles: Current developments

1,2,3-Triazoles are important five-membered heterocyclic scaffold due to their extensive biological activities. This framework can be readily obtained in good to excellent yields on the multigram scale through click chemistry via reaction of aryl/alkyl halides, alkynes and NaN₃ under ambient conditions. It has been an emerging area of interest for many researchers throughout the globe owing to its immense pharmacological scope. The present work aims to summarize the current approaches adopted for the synthesis of the 1,2,3-triazole and medicinal significance of these architectures as a lead structure for the discovery of drug molecules such as COX-1/COX-2 inhibitors (celecoxib, pyrazofurin), HIV protease inhibitors, CB1 cannabinoid receptor antagonist and much more which are in the pipeline of clinical trials. The emphasis has been given on the major advancements in the medicinal prospectus of this pharmacophore for the period during 2008–2016.     

Engineering biological systems with synthetic RNA molecules

RNA molecules play diverse functional roles in natural biological systems. There has been growing interest in designing synthetic RNA counterparts for programming biological function. The design of synthetic RNA molecules that exhibit diverse activities, including sensing, regulatory, information processing, and scaffolding activities, has highlighted the advantages of RNA as a programmable design substrate. Recent advances in implementing these engineered RNA molecules as key control elements in synthetic genetic networks are highlighting the functional relevance of this class of synthetic elements in programming cellular behaviors.     

Synthesis of New Thiazolidinone Nucleoside Analogues

Abstract

The synthesis of new thiazolididone nucleoside analogues is described. Among the different proposed synthetic pathways, the condensation of various nucleic bases using TMSOTf and Et₃N as coupling reagents on a key sulfoxide thiazolidinone intermediate led to the desired compounds in a one-pot procedure. Analytical data and NMR studies confirmed the proposed structure assignment for these compounds.     

Solid-phase synthesis of triple-helical collagen-model peptides

Summary The triple-helical conformation of collagen has been proposed to be important for mediation of cellular activities, such as adhesion and activation, extracellular matrix assembly, and enzyme function. We have developed synthetic protocols that allow for the study of biological activities of specific collagen sequences in triple-helical conformation. These methods primarily involve solid-phase assembly and covalent linkage of three peptide chains. The resultant triple-helical peptides have sufficient thermal stabilities to permit structural and biological characterization under physiological conditions. The present article critically reviews the various approaches for constructing synthetic triple-helices.This paper is based on a presentation given at the Symposium on Peptide Structure and Design as part of the 31st Annual ACS Western Regional Meeting held in San Diego, CA, USA, October 18–21, 1995.     

Mechanisms of lysophosphatidic acid production

Lysophosphatidic acid is one of the most attractive phospholipid mediator with multiple biological functions and is implicated in various human diseases. In the past ten years much has been learned about the physiological roles of LPA through series of studies on LPA actions and its receptors. However, the molecular mechanisms of LPA have been poorly understood. LPA is produced in various conditions both in cells and in biological fluids, where multiple synthetic reactions occur. At least two pathways are postulated. In serum and plasma, LPA is mainly converted from lysophospholipids. By contrast, in platelets and some cancer cells, LPA is converted from phosphatidic acid. In each pathway, at least two phospholipase activities are required: phospholipase A1 (PLA1)/PLA2 plus lysophospholipase D (lysoPLD) activities are involved in the first pathway and phospholipase D (PLD) plus PLA1/PLA2 activities are involved in the second pathway. Now multiple phospholipases are identified that account for PLA1, PLA2, PLD, and lysoPLD activities. In the absence of specific inhibitors and genetically modified animals and individuals, the contribution of each phospholipase to LPA production can not be easily determined. However, apparently certain extracellular phospholipases such as secretory PLA2 (sPLA2-IIA), membrane-associated PA-selective PLA1 (mPA-PLA1), lecithin-cholesterol acyltransferase (LCAT), and lysoPLD are involved in LPA production.     

Isolation and structure of a pseudopeptide gamma-L-glutamyl-L-aspartic acid from Datura stramonium that impairs learning retention in mice

Datura stramonium contains a compound that impairs learning retention in mice. It has been purified to homogeneity and its structure has been established as that of a gamma-L-glutamyl-L-aspartate. The biological activity of this pseudodipeptide has been found to be identical with that of the corresponding synthetic one. It has also been compared to those of various synthetic di- and tripeptides containing L- and/or D-enantiomers of the constitutive amino acids. The results show that the activity is associated with a peptidic structure containing only one type of enantiomer.     

POSH is involved in Eiger-Basket （TNF-JNK） signaling and embryogenesis in Drosophila

TNFα can trigger different signaling pathways, including the JNK pathway, to regulate various biological functions such as cell death, differentiation and proliferation. The scaffold protein POSH(Plenty of SH3 Domains)has been shown to be an important regulator of the JNK pathway, but whether it is involved in TNF-signaling has not been reported.Although POSH has been implicated to play a role in development in zebrafish,it has not been studied in null mutants and the underlying mechanism of its effects is still not clear.In this study,we provide evidence that the JNK pathway scaffold protein,POSH,is involved in TNF(Eiger)signaling in Drosophila.POSH is likely to act downstream of dTAB2 and upstream of dTAK1 in the TNF-JNK signaling pathway.In addition,we found that POSH is essential during Drosophila embryogenesis,including epidermal dorsal closure,similar to other JNK pathway components such as Slipper,Hemipterous,and Basket. We observed defects in F-actin accumulation and adherens junction formation during dorsal closure in different posh null mutants, suggesting that POSH is required for epidermal cell migration and cell-shape change during epidermal dorsal closure.     

Structural and Biological Diversity of Cyclic Octadecanoids,Jasmonates, and Mimetics

The jasmonate family of plant signaling compounds comprises biologically highly active cyclopentenones (for example, 12-oxo-phytodienoic acid) (12-OPDA) and cyclopentanones (for example, jasmonic acid) (JA) of related origin via the octadecanoid pathway, and structure. Among others, their biological activities include a broad range of defense-related reactions. Several lines of evidence indicate both common and different biological responses mediated by 12-OPDA and/or JA, suggesting the existence of at least two separate structure-activity groups. Based on the structure of a bacterial phytotoxin, coronatine, with similar biological activities compared with jasmonates, indanoyl isoleucine conjugates have been designed as functional synthetic mimics of octadecanoid-derived signals. The structural diversity of naturally occurring jasmonate-related compounds and synthetic mimics is discussed with respect to their corresponding biological activities. Novel strategies for the synthesis of various indanoyl isoleucine conjugates will be presented.