Rajani Chauhan

Synthesis of Pyrazole Derivatives Possessing Anticancer Activity: Current Status

Abstract Pyrazole is a versatile lead compound to design potent bioactive molecules for drug discovery and development, particularly in cancer therapy. The aim of this review is to present the most recent deeds in the field of synthetic route made for functionalized pyrazole derivatives active against cell proliferation disease. The review article covers the synthesis of 1H-pyrazole, synthesis of N-substituted pyrazoles, synthesis of pyrazolopyrazoles, and synthesis of pyrazoles fused with a naturally occurring moiety. Some of these reported compounds have passed the preclinical or initial-phase clinical trials for their anticancer activity. GRAPHICAL ABSTRACT

Anticancer Activity of Pyrazole via Different Biological Mechanisms

Abstract In the past few years pyrazole derivatives have attracted increasing attention because of their numerous potential pharmacological applications. Changes in their structure have offered a high degree of diversity that has proven useful for the development of new medicinal agents with improved potency and less toxicity. This review focuses on the recent developments in pyrazole along with their structure–activity relationship (SAR), particularly for anticancer activity. The review covers SAR for active pyrazole molecules such as cyclin dependent kinase (CDK) inhibitor (modulator), aurora kinase inhibitors (modulator), break point cluster region-Abelson (BCR-ABL) tyrosine kinase inhibitors (modulator), heat shock protein (HSP 90) inhibitors (modulator), polo-like kinase inhibitors (modulator), cyclo-oxygenase (COX) and lypo-oxygenase (LOX) inhibitors (modulator), epithelial growth factor receptor (EGFR) inhibitors (modulator), reticular activating system–neuro endocrine tumor (Ras-Net) ETS-like transcription factor (Elk-3) pathway inhibitors (modulator), and DNA binding agent. GRAPHICAL ABSTRACT

Transition metal-free one-pot synthesis of nitrogen-containing heterocycles

One-pot heterocyclic synthesis is an exciting research area as it can open routes for the development of otherwise complex transformations in organic synthesis. Heterocyclic compounds show wide spectrum of applications in medicinal chemistry, chemical biology, and materials science. These heterocycles can be generated very efficiently through highly economical and viable routes using one-pot synthesis. In particular, the metal-free one-pot synthetic protocols are highly fascinating due to several advantages for the industrial production of heterocyclic frameworks. This comprehensive review is devoted to the transition metal-free one-pot synthesis of nitrogen-containing heterocycles from the period 2010–2013.Graphical abstract

Entrapment of ketorolac tromethamine in polymeric vehicle for controlled drug delivery.

The most common method for applying a drug in to the eye is to formulate the drug in the form of an eye drop, but this method is not considered ideal for ocular delivery of drug because of poor bioavailability arising from precorneal loss processes, this loss of drug from the precorneal area is a net effect of drainage, tear secretion and noncorneal absorption. Following the above lead we tried to improve the ocular bioavailability by increasing the corneal contact time and the feasible way was to formulate a drug with mucoadhesive/viscosity imparting agents. The adhesive strength of various polymers on corneal surface was studied with the help of self modified Franz diffusion cell and freshly excised goat/bovine cornea. The polymers hydroxypropylmethylcellulose, carboxymethylcellulose sodium, Eudragit type E/RL/RS, Carbopol ETD 2020 and Carbopol 934 National Formulary were formulated with drug, ketorolac tromethamine. The adhesive strength of polymers on corneal surface and permeation characteristics of drug through cornea were investigated by using above said formulations. Eudragit type E/RL/RS did not show any improvement in mucoadhesion, but the formulations containing Carbopol ETD 2020 and Carbopol 934 national formulary showed good mucoadhesion on corneal surface in the concentration as low as 0.75%. The mucoadhesive strength was also evaluated using the combination of Carbopol acrylates/C 10-30 alkylacrylate with allylpentaerithrital and preservative benzalkonium chloride, which also resulted in good mucoadhesion with improved corneal permeation. Observations made in this study indicate the potentiality of the ophthalmic formulations containing mucoadhesive/viscosity imparting agents.

Synthesis of Pyrimidino Derivatives: Potent Antimicrobial Candidates

A series of pyimidino derivatives including 4,5-dihydro-5-(1H-indol-1-yl)-6-(phenyl)-4-(4-substituted phenyl) pyrimidine-2-(1H)-one/thione and 4,5-dihydro-4-(3,4,5-trimethoxyphenyl)-6-phenyl-5-[3-(substitute-1-yl))-1H-indol-1-yl]pyrimidin-2(1H)-one/thione have been synthesis and their antimicrobial activity has been assessed in order to study the antimicrobial synergism of indole and benzene nuclei in single molecule. The structures of synthesized compounds were confirmed by IR, NMR and mass spectroscopy data. Antimicrobial activity assessment gives comparable to excellent results against all test microbes. It is concluded that nuclei separately possessing antimicrobial activity exhibit synergism when combined in a single molecule.

2-D QSAR model development for α-amino suberic acid derivatives as a novel anticancer agent

Structure activity relationship has been reported for 34 compounds derived from α-amino suberic acid. Compounds in this class typically inhibit human histone deacetylase by hyperacetylation of histone protein in both normal and cancer cells induce expression of p21 and differentiate surviving cancer cells to a non-proliferating phenotype. In the present study, quantitative structure activity relationship study was performed on a series of novel α-amino suberic acid derivatives as inhibitors of histone deacetylase. Multiple linear regression analysis was performed to derive quantitative structure activity relationship models which were further evaluated internally as well as externally for the prediction of activity. The best quantitative structure activity relationship model for multiple linear relationship analysis was selected with a correlation coefficient (r2) of 0.855, cross validation r2 (CV) 0.809 and the standard error 0.287. Further partial least square and neural network analysis were also performed for partial least square analysis correlation coefficient (r2) 0.876, CV r2 0.756, standard error 0.287 for neural networking analysis R2 of training set 0.861, R2 of test set 0.661. All of them generated comparable results which prove that the model formed is sound and has good predictability.

RECENT CHEMICAL ADVANCEMENTS OF PYRAZOLE MOIETY IN ANTICANCER THERAPY

Pyrazole moiety is one of the main scaffold for many anticancer drug candidates.Many pyrazole derivatives have been synthesized which shows their activity against different leukemia cell line, non-small cell lung cancer, colon cancer, prostate cancer, CNS cancer, renal cancer, breast cancer, ovarian cancer and cervix cancer cell line. Literature survey revealed that they have been implemented as antitumor, antileukemic and antiproliferative agent beside their capability to inhibit different types of enzymes which plays important roles in cell division.