Pankaj Kumar Sonar

4-Thiazolidinones: The advances continue.

The diversity in the biological response of 4-thiazolidinones has attracted the attention of many researchers to explore this framework for its potential. It is, therefore, of prime importance that the study of this topic and the development of new synthetic strategies should be based on the most recent knowledge, emerging from the latest research. This review is an endeavor to highlight the progress in the chemistry and biological activity of the 4-thiazolidinones, predominantly after 2006. The last section of the review encompasses the various patents granted on 4-thiazolidinone analogs/derivatives with World Intellectual Proprietary Organization (WIPO) and United State Patent Trademark Office (USPTO), particularly in the duration of the year 2000 to the year 2012.

Synthesis of 1,3,5-trisubstituted pyrazoline nucleus containing compounds and screening for antimicrobial activity

In this study, a novel series of heterocyclic compounds containing pyrazoline nucleus has been synthesized. The compounds were synthesized in two steps. Chalcone was synthesized in the first step by Claisen-Schmidt reaction, using 1-acetylnaphthalene and p-nitro benzaldehyde as reactants. In the second step, the chalcone was cyclized in an acidic medium with some hydrazine derivatives to form pyrazolines. All the compounds were characterized by physical, chromatographic, spectroscopic, and elemental analysis and evaluated in vitro for antimicrobial activity against nine microorganisms by cup-plate method. The minimum inhibitory concentration of all the compounds was determined by tube dilution method. All the compounds exhibited higher antibacterial activity as compared to the antifungal activity. Compound 5g (3-Naphthalen-1-yl-1-(2-nitro-phenyl)-5-(4-nitro-phenyl)-4,5-dihydro-1H-pyrazole) exhibited maximum antibacterial and antifungal activity and may be designated as the most potent member of the series, with 2-nitrophenyl group at N-1 position of the 2-pyrazoline ring.

Isolation, Characterization and Activity of the Flowers of Rhododendron arboreum (Ericaceae)

The flowers of Rhododendron arboreum have been reported to possess certain polyphenolic compounds. Thus, this study was aimed at the anti-microbial and phytochemical screening of the flowers. Important bioactive agents like steroids, saponins and flavonoids were detected in the flowers. Quercetin (a flavonoid) was isolated from the diethyl ether fraction of alcoholic extract by solvent-solvent extraction method. Isolated quercetin was identified and characterized by chemical tests, M.P., TLC, paper chromatography (with authentic marker) and spectroscopic methods like UV-Visible, FT-IR, 1HNMR, 13CNMR and Mass spectroscopy. The anti-microbial activity of the alcoholic and aqueous extract and isolated quercetin were investigated against five bacterial and two fungal strains by agar well-diffusion method. The activity was found to be concentration dependent. Ethanolic extract was found to be more active in comparison to the aqueous extract. Hence, isolation was done with ethanolic extract. The lowest effective concentration of quercetin was found to be 12.5 mg/ml against S. aureus and P. aeruginosa. Both extracts and isolated quercetin were found ineffective against fungal strains. Quercetin may be one of the components responsible for the observed anti-microbial activity of the plant.

4-Thiazolidinone and 1-thia-3,4,9-triaza fluorene conjugates: synthesis, characterization and antimicrobial screening

Some novel 4-thiazolidinone derivatives have been synthesized by the condensation of isatin/5-chloroisatin with thiosemicarbazide to yield thiosemicarbazones, which were then cyclized to form corresponding thia-3,4,9-triaza-fluoren-2-ylamines. These were reacted with substituted aldehydes to give corresponding Schiff bases, which were cyclized using thioglycolic acid in the presence of zinc chloride to obtain the 4-thiazolidinone derivatives. All the synthesized compounds were characterized by spectral (IR, MS and NMR) and elemental analysis. The compounds were screened for their antibacterial activity against Gram-positive bacteria (B. subtilis, S. aureus, B. pumilus and M. luteus), Gram-negative bacteria (P. aeruginosa, E. coli and P. fluorescens) and for antifungal activity against A. niger and P. chrysogenum by agar-diffusion method. The minimum inhibitory concentrations of these compounds were also determined by tube dilution method. The antimicrobial effectiveness of all the compounds was found to be concentration dependent. Two compounds—2-methyl-3-(1-thia-3, 4, 9-triaza-fluoren-2-yl)-thiazolidin-4-one (7aI) and 2-naphthalen-1-yl-3-(1-thia-3, 4, 9-tri aza-fluoren-2-yl)-thiazolidin-4-one (7aII)—exhibited good antibacterial activity. The antibacterial activity of all the compounds was found to be better than the antifungal activity.

Syntheses, Characterization and Antimicrobial Evaluation of Some 1, 3, 5-Trisubustituted Pyrazole Derivatives

A series of 1, 3, 5-trisubustituted pyrazole derivatives were synthesized and screened for antimicrobial activity. The compounds (2j-o) were evaluated against two gram-positive and two gram-negative bacteria and one fungus, at concentrations of 10 µg/mL and 50 µg/mL. The compounds were founds to be inactive against P. aeruginosa and A. niger but exhibited moderate activity against B. subtilis, E. coli and S. aureus. It can be concluded that the newly synthesized compounds possess promising antimicrobial activity.

Novel 4-Thiazolidinone Derivatives as Anti-Infective Agents: Synthesis, Characterization, and Antimicrobial Evaluation

A series of new 4-thiazolidinone derivatives was synthesized, characterized by spectral techniques, and screened for antimicrobial activity. All the compounds were evaluated against five Gram-positive bacteria, two Gram-negative bacteria, and two fungi, at concentrations of 50, 100, 200, 400, 800, and 1600 µg/mL, respectively. Minimum inhibitory concentrations of all the compounds were also determined and were found to be in the range of 100–400 µg/mL. All the compounds showed moderate-to-good antimicrobial activity. Compounds 4a [2-(4-fluoro-phenyl)-3-(4-methyl-5,6,7,8-tetrahydro-quinazolin-2-yl)-thiazolidin-4-one] and 4e [3-(4,6-dimethyl-pyrimidin-2-yl)-2-(2-methoxy-phenyl)-thiazolidin-4-one] were the most potent compounds of the series, exhibiting marked antimicrobial activity against Pseudomonas fluorescens, Staphylococcus aureus, and the fungal strains. Thus, on the basis of results obtained, it may be concluded that synthesized compounds exhibit a broad spectrum of antimicrobial activity.

Schizonticidal antimalarial sesquiterpene lactones from Magnolia champaca (L.) Baill. ex Pierre: microwave-assisted extraction, HPTLC fingerprinting and computational studies

Abstract The present study explored the schizonticidal potential of traditionally used Magnolia champaca (L.) Baill. ex. Pierre flowers, identifying constituents of interest. The extraction of phytoconstituents was carried out by microwave-assisted technique, isolated via column chromatography, and characterised by various physicochemical, spectral (IR, 1H-NMR and Mass) and chromatographic (HPTLC) techniques. Both the isolated compounds (parthenolide and costunolide diepoxide) exhibited potent schizonticidal antimalarial activity during primary screening in rodent models, with maximum parasitaemia suppression (85.18% and 83.65%, respectively) at a dose of 20 mg/kg body weight when compared to the standard drugs chloroquine and artesunate. In silico techniques were employed to identify the probable biological target and mechanism of action of these isolated compounds. Molecular docking studies also predicted the binding orientations and multi-targeted action of these compounds, in particular costunolide diepoxide with maximum affinity towards SERCA and DHFR proteins. Additionally, favourable in silico ADMET parameters were envisaged through various computational programmes.

Phytochemical, chromatographic and spectroscopic investigation of Carum copticum seeds and their potential as immunomodulatory agents

Abstract Context: Carum copticum seeds have been prescribed in the traditional system of medicine for the treatment of immune disorders, such as asthma and rheumatism. Objective: The objective of this study was to determine immunomodulatory effects of the alcoholic extract and isolated compounds in Swiss albino mice. Materials and methods: Seeds of C. copticum were extracted with 95% v/v alcohol. The immunomodulatory activity of the crude extract was evaluated at the doses of 100, 300, and 500 mg/kg body weight of mice, administered in mice once daily (orally) for 25 days. Volatile oil of C. copticum was isolated by steam distillation and was characterized by GLC and HPLC. Bio-assay-guided fractionation and isolation were carried out and the isolated compounds were characterized and subjected to immunomodulatory activity studies. Results: The n-hexane fraction yielded p-cymene, carvacrol, and α-pinene. The LD50 value of the crude extract was found to be 4500 mg/kg and the values reported for p-cymene, carvacrol, and α-pinene in the literature were 4750, 810, and 3700 mg/kg, respectively. The oral administration of crude extract, n-hexane fraction (HEF), and isolated oils at the dose of 500, 150, and 50 mg/kg body weight, respectively, showed a significant increase in the HA titers, DTH-response, and phagocytosis. The stimulatory effect observed, on humoral and cellular immunity, was compared with the standard (levamisole treated) and control groups. Discussion and conclusion: The results obtained in the study endorse the traditional use of the seeds of C. copticum and the isolated constituents act as immunostimulants.

Structural Insights into the Molecular Design of HER2 Inhibitors

Background: The present study was aimed at designing some potential candidates as HER2 inhibitors used in breast cancer. Methods: An energy optimized pharmacophore (E-pharmacophore) model was developed and used to screen the molecular databases (such as ASINEX and NCI databases) against a six site (ADHRRR) hypothesis. The shape similarity of the retrieved hits was calculated and

Facile synthesis, molecular docking and toxicity studies of 4-Phenyl-3-phenylamino-4H-[1,2,4]thiadiazol-5-one analogs as GABAA receptor agonists

A series of 4-Phenyl-3-phenylamino-4H-[1,2,4]thiadiazol-5-one derivatives was synthesized by a simple method and their structures were established by physical and spectroscopic methods like infrared, mass and nuclear magnetic resonance spectroscopy. Elemental formulae of all the compounds were determined by elemental analysis and compared with the calculated value. Log P value and in vitro hydrolysis, in simulated gastric fluid and simulated intestinal fluid, for all the compounds were determined by standard methods. Synthesized 1, 2, 4-thiadiazolines were screened for their anticonvulsant activity against maximal electroshock method and isoniazid induced seizures. All the compounds showed good anticonvulsant activity. The compound 4-(3,4-dichloro-phenyl)-3-(3,4-dichloro-phenylamino)-4H-[1,2,4]thiadiazol-5-one (3a) was found to be the most potent member of the series. Molecular docking studies of the synthesized compounds depicted their stable ligand–receptor complex conformation with the typical binding pocket of γ-aminobutyric acid A receptor protein. Compound 3a confined its effect in the molecular docking studies also with non-covalent interactions with Tyr 157, Phe 200 and Tyr 205, the key interacting residues of γ-aminobutyric acid A receptor protein 4COF. In silico absorption, distribution, metabolism and elimination performance of all the compounds also appear to favour anticonvulsant effect. “LAZAR” and “OSIRIS” property explorer predicted nontoxic, nonmutagenic, noncarcinogenic, etc. nature for all the compounds. In conclusion, some γ-aminobutyric acid A receptor agonists have been synthesized in this study with promising drug-like properties, which merit further development.