Quinoline: A versatile heterocyclic.

Quinoline or 1-aza-naphthalene is a weak tertiary base. Quinoline ring has been found to possess antimalarial, anti-bacterial, antifungal, anthelmintic, cardiotonic, anticonvulsant, anti-inflammatory, and analgesic activity. Quinoline not only has a wide range of biological and pharmacological activities but there are several established protocols for the synthesis of this ring. The article aims at highlighting these very diversities of the ring.

Microwave assisted one pot synthesis of some pyrazole derivatives as a safer anti-inflammatory and analgesic agents.

A series of pyrazolo[3,4-b]quinolines have been synthesized using one-pot water mediated synthetic route under microwave irradiation involving the condensation of 2-chloroquinoline-3-carbaldehydes with semicarbazide or 2,4-dinitrophenyl hydrazine. The compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation actions. The pharmacological evaluation showed that the compounds are good at inhibiting edema induced by carrageenan and also showed prominent analgesic activity with lesser GI toxicity as indicated by severity index and LPO values.

Anti-inflammatory and antimicrobial activity of 4,5-dihydropyrimidine-5-carbonitrile derivatives: their synthesis and spectral elucidation.

Thirteen new 6-(1-H-indole-2-yl)-4-oxo-2-[2-(substituted-benzylidene)-hydrazinyl]-4,5-dihydropy-rimidine-5-carbonitrile derivatives were synthesized. The title compounds, hydrazones, were synthesized by reaction of hydrazine group of 2-hydrazinyl-4-(1-H-indole-2-yl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (2) with different substituted aromatic aldehydes using a mixture (2:8, v/v) of glacial acetic acid and alcohol. The required intermediate compound 2 was synthesized from 2-mercapto-4-(1-H-indole-2-yl)-6-oxo-1,6-dihy-dropyrimidine-5-carbonitrile 1 upon nucleophilic attack by the hydrazine hydrate. Compound 1 was synthesized by modified Biginelli condensation method using indole-3-carbaldehyde, ethyl cyanoacetate and thiourea. The compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic and antimicrobial actions. Among the newer derivatives, one compound i.e., 6-(1-H-indole-2-yl)-4-oxo-2-[2-(2,6-dichlorobenzylidene)-hydrazinyl]-4,5-dihydropyrimidine-5-carbonitrile (7) emerged as lead compound having 71.14% inhibition of edema and 12.5 microg/mL MIC against both bacterial and fungal strains.

3D QSAR of aminophenyl benzamide derivatives as histone deacetylase inhibitors.

The article describes the development of a robust pharmacophore model and the investigation of structure activity relationship analysis of 48 aminophenyl benzamide derivatives reported for Histone Deacetylase (HDAC) inhibition using PHASE module of Schrodinger software. A five point pharmacophore model consisting of two aromatic rings (R), two hydrogen bond donors (D) and one hydrogen bond acceptor (A) with discrete geometries as pharmacophoric features was developed and the generated pharmacophore model was used to derive a predictive atom-based 3D QSAR model for the studied dataset. The obtained 3D QSAR model has an excellent correlation coefficient value (r(2)=0.99) along with good statistical significance as shown by high Fisher ratio (F=631.80). The model also exhibits good predictive power confirmed by the high value of cross validated correlation coefficient (q(2) = 0.85). The QSAR model suggests that hydrophobic character is crucial for the HDAC inhibitory activity exhibited by these compounds and inclusion of hydrophobic substituents will enhance the HDAC inhibition. In addition to the hydrophobic character, hydrogen bond donating groups positively contributes to the HDAC inhibition whereas electron withdrawing groups has a negative influence in HDAC inhibitory potency. The findings of the QSAR study provide a set of guidelines for designing compounds with better HDAC inhibitory potency.