Abhishek Kumar Jain

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.

Synthesis and antibacterial evaluation of 2-substituted-4,5-diphenyl-N-alkyl imidazole derivatives

Objective: To synthesis 2-substituted-4,5-diphenyl-N-alkyl imidazole derivatives, and evaluate their antibacterial activity. Methods: A mixture of benzil (10 mmol) and ammonium acetate (0.1 mol) (immediately fused) in glacial acetic acid (25 mL) was stirred at 80-100℃ for 1 h under nitrogen atmosphere (to prevent incorporation of any atmospheric impurities and moisture). Substituted aldehydes (10 mmol) in glacial acetic acid (5 mL) was added drop-wise over a period of 15-20 min at the same temperature and stirred for another 4 h, the progress of the reaction was monitored by TLC test using ethyl acetate as eluent. The newly synthesized compounds were characterized by IR, 1HNMR, 13CNMR and by mass spectroscopy. Results: All the synthesized compounds were confirmed by spectroscopical techniques and evaluated for antimicrobial activity against Staphylococcus aureus (S. aurius), Bacilus subtilus (B. subtilus), and Escheria coli (E. coli). These compounds showed antibacterial activity (zone of inhibition) against S. aurius ranged from 3 mm to 9 mmin diameter, B. subtilus, 4-8 mm, and E. coli 5-12 mm. Out of 2a-2e, only 2a and 2b showed some sort of activity but none of them had considerable activity compared with that of the standard. Conclusions: All the synthesized compounds show moderate activity against the tested bacteria S. aurius, B. subtilus, and E. coli. So, further structural modification is necessary to improve the antibacterial action of 2-substituted-4,5-diphenyl-N-alkyl imidazole derivatives.

Design, synthesis, and evaluation of thiazolidinone derivatives as antimicrobial and anti-viral agents.

A series of 1,3‐thiazolidin‐4‐one derivatives were prepared by the reaction of respective aromatic amine, aromatic aldehyde, and thioglycolic acid in dry benzene/toluene. The newly synthesized compounds were characterized on the basis of elemental analysis, IR, 1HNMR, and mass spectra. The newly synthesized final compounds were evaluated for their in vitro antibacterial, antifungal, and anti‐viral activities. Preliminary results indicated that some of the compounds demonstrated antibacterial activity in the range of 7–13 μg/mL, antifungal activity in the range of 13–17 μg/mL, comparable with the standard drugs, ciprofloxacin and fluconazole. Structure–activity relationship studies revealed that the nature of the substituents at the 2 and 3 positions of the thiazolidinone nucleus had a significant impact on the in vitro antimicrobial and anti‐viral activity of these classes of agents.

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.

Prediction of antiproliferative activity of some flavone derivatives: QSAR study.

Quantitative structure–activity relationship (QSAR) has been established for 32 oxime- and methyloxime-containing flavone and isoflavone derivatives having antiproliferative activity. Multiple linear regressions were used to generate the relationship between biological activity and calculated descriptors. Model with good statistical qualities was developed using the software VLIFE MDS 2.0. Validation of the model was done by cross-validation, randomization, and external test set prediction. On the basis of the QSAR model, we designed a new series of compounds and calculated the activity and found that the compounds were more potent than the existing compounds.Graphical AbstractQSAR studies of flavone and isoflavone derivatives. The negative coefficient of SdOi indicated that its increase is detrimental to antiproliferative activity. The positive coefficient of QMDMg showed that the magnitude of dipole is responsible for the activity.

QSAR study of 2,4-disubstituted phenoxyacetic acid derivatives as a CRTh2 receptor antagonists

In pursuit of better CRTh2 receptor antagonist agents, QSAR studies were performed on a series of 2,4-disubstituted phenoxyacetic acid derivatives. Stepwise multiple linear regression analysis was performed to derive QSAR models which were further evaluated for statistical significance and predictive power by internal and external validation. The best QSAR model was selected; having the correlation coefficient R = 0.904, standard error of estimation SEE = 0.456 and the cross validated squared correlation coefficient Q2 = 0.739. Predictive ability of the selected model was also confirmed by the leave one out cross validation method and by leave 33 % out Q2 = 0.688. The QSAR model indicates that the descriptors (logP, SI3, LM, and DVZ) play an important role in the CRTh2 receptor antagonist activities. Results of the present study may be useful in the designing of more potent 2,4-disubstituted phenoxyacetic acid derivatives as CRTh2 receptor antagonist agents.

Prediction of anti-HIV activity and cytotoxicity of pyrimidinyl and triazinyl amines: A QSAR study

A QSAR study on a series of pyrimidinyl and triazinyl amines was performed to explore the physico-chemical parameters responsible for their anti-HIV activity and cytotoxicity. Physico-chemical parameters were calculated using WIN CAChe 6.1. Stepwise multiple linear regression analysis was carried out to derive QSAR models which were further evaluated for statistical significance and predictive power by internal and external validation. The selected best QSAR models showed correlation coefficient R of 0.914 and 0.901, and cross-validated squared correlation coefficient Q2 of 0.685 and 0.691 for anti-HIV activity and cytotoxicity, respectively. The developed significant QSAR model indicates that hydrophobicity of the whole molecule plays an important role in the anti-HIV activity and cytotoxicity of pyrimidinyl and triazinyl amine derivatives. When hydrophobicity is increased, anti-HIV activity of the present series of compounds is decreased leading to high cytotoxicity.