Novel Glycopyrrolidine Compounds Inhibit Human Cancer Cell Proliferation and Induce Apoptotic Mode of Cell Death.

Spirocyclic compounds, present in a number of bioactive natural alkaloids, are cyclic systems containing one carbon atom common to two rings. A highly regioselective glycopyrrolidine compound library was synthesized using 1,3-dipolar cycloaddition method, and its efficacy was tested on cell lines representing most commonly occurring cancers and the molecular mechanism of cell death deciphered. Results showed that among the 16 compounds screened, RPRR210 showed the most potent anticancer activity and induced cell cycle arrest, inhibited migration, caused cell death by inducing apoptosis through the intrinsic pathway, and were nontoxic to normal cells.

β-lactam substituted polycyclic fused pyrrolidine/pyrrolizidine derivatives eradicate C. albicans in an ex vivo human dentinal tubule model by inhibiting sterol 14-α demethylase and cAMP pathway.

Background: Further quest for new anti-fungal compounds with proven mechanisms of action arises due to resistance and dose limiting toxicity of existing agents. Among the human fungal pathogens C. albicans predominate by infecting several sites in the body and in particular oral cavity and root canals of human tooth.

Bioactivity Studies of β-Lactam Derived Polycyclic Fused Pyrroli-Dine/Pyrrolizidine Derivatives in Dentistry: In Vitro, In Vivo and In Silico Studies.

The antibacterial activity of β-lactam derived polycyclic fused pyrrolidine/pyrrolizidine derivatives synthesized by 1, 3-dipolar cycloaddition reaction was evaluated against microbes involved in dental infection. Fifteen compounds were screened; among them compound 3 showed efficient antibacterial activity in an ex vivo dentinal tubule model and in vivo mice infectious model. In silico docking studies showed greater affinity to penicillin binding protein.

Synthesis and antibacterial property of pyrrolopyrano quinolinones and pyrroloquinolines.

Synthesis of a series of novel pyrroloquinolinone and pyrroloquinoline derivatives has been accomplished by intramolecular domino Knoevenagel hetero Diels-Alder reaction and intramolecular imino Diels-Alder reaction. These compounds were evaluated for their antibacterial activity against bacterial pathogens using disc diffusion and broth dilution methods. The efficacy of binding of these compounds to gyrase, an enzyme known to play a key role in bacterial replication is examined by studying its supercoiling and relaxation and also its gene expression using PCR method.

Synthesis and antibacterial property of quinolines with potent DNA gyrase activity.

Synthesis of a series of novel tetrahydroquinoline annulated heterocycles has been accomplished by intramolecular imino and bisimino Diels-Alder reaction. These compounds were evaluated for their antibacterial activity. All the synthetic compounds, exhibited good antibacterial activity against microorganisms of which one of them 7 was found to be as active as the antibiotic ciplofloxacin and is found to have MIC value of 2.