Pallavi Rao

InCl3-catalysed synthesis of 2-aryl quinazolin-4(3H)-ones and 5-aryl pyrazolo[4,3-d]pyrimidin-7(6H)-ones and their evaluation as potential anticancer agents.

A convenient and practical methodology for the synthesis of 2-aryl quinazolin-4(3H)-ones by the condensation of o-aminobenzamides with aromatic aldehydes under mild conditions using catalytic InCl(3) with good yields and high selectivities. This method has been extended for the synthesis of 5-aryl pyrazolo[4,3-d]pyrimidin-7(6H)-ones which have potential applications in medicinal chemistry. Many of these compounds were evaluated for their anti-proliferative properties in vitro against four cancer cell lines and several compounds were found to be active. Further in vitro studies indicated that inhibition of sirtuins could be the possible mechanism of action of these molecules.

Oral dosing in adult zebrafish: Proof-of-concept using pharmacokinetics and pharmacological evaluation of carbamazepine

BACKGROUND AND METHODS We describe a method for obtaining pharmacokinetics (PK) and pharmacology data from adult zebrafish in terms of mg/kg using a novel method of oral administration. Using carbamazepine (CBZ) as a test drug, we employed dried blood spot (DBS) cards to enable drug quantification for PK; and we evaluated the pharmacological anxiolytic effect using novel tank test. RESULTS The PK study confirmed the presence of CBZ in both blood and brain and the behavioural study showed dose dependent anxiolytic effect. The reproducibility of oral dosing was confirmed by the fact that the results obtained in both the experiments had negligible errors. CONCLUSIONS This report enables a novel approach for optimizing the utility of zebrafish in drug discovery and drug delivery research.

Synthesis of novel therapeutic agents for the treatment of multiple sclerosis: a brief overview.

Multiple sclerosis (MS) often results in chronic inflammatory and autoimmune disorders, and recent developments in understanding the disease pathogenesis has lead to newer therapeutic options for the treatment of the disease. The development of small molecule drugs with improved efficacy, better tolerability, and oral administration has received a new impetus with the discovery of newer classes of drugs. In this review, we have summarized the hitherto known synthetic strategies of fingolimod, laquinimod, cladribine, and teriflunomide reported in the literature which are the key small molecules and the first oral drug candidates for MS in various stages of clinical development or have been launched in the market.

Click chemistry route to tricyclic monosaccharide triazole hybrids: design and synthesis of substituted hexahydro-4H-pyrano[2,3-f][1,2,3]triazolo[5,1-c][1,4]oxazepines

A click chemistry approach to novel tricyclic monosaccharide triazole hybrids, namely, aryl substituted hexahydro-4H-pyrano[2,3-f][1,2,3]triazolo[5,1-c][1,4]oxazepine derivatives from an intramolecular 1,3-dipolar cycloaddition of 6-azido-4-O-propargyl glycopyranosides has been reported.

Correlation of pharmacokinetics and brain penetration data of adult zebrafish with higher mammals including humans

INTRODUCTION Adult zebrafish pharmacology is evolving rapidly for creating efficacy and safety models for drug discovery. However, there is very limited research in understanding pharmacokinetics (PK) in adult zebrafish. Methods for understanding PK will help in conducting pharmacokinetic - pharmacodynamic (PK-PD) correlations and improving the quality and applicability of data obtained using zebrafish. METHODS We conducted adult zebrafish PK and brain penetration studies on two known compounds (irinotecan and lorcaserin) with distinct PK and brain penetration properties using validated LCMS/MS method. Irinotecan was studied at a dose of 100mg/kg i.p. and levels of the parent drug and active metabolite SN-38 were measured. Loracserin was studies at a dose of 10mg/kg by two routes i.p. and p.o. RESULTS Zebrafish PK and brain penetration profiles for both compounds were very similar to that of higher mammals including humans. Irinotecan was metabolised to SN-38 in ratios similar to ratios seen in other species and the compound had long half life with very low brain penetration in our studies. Loracasin was highly permeable in brain as compared to the exposure in blood, with long half life and high relative bioavailability, similar to other mammalian species including humans. DISCUSSION Adult zebrafish PK studies are relatively an unexplored area of zebrafish research. The zebrafish data for key parameters of irinotecan and loracserin shows a high correlation to the data from higher species, including human. This report explores and discusses the use of adult zebrafish as a predictive PK tool for higher animal studies.