Paranjay Parikh

Bio: Paranjay Parikh is an academic researcher from Charotar University of Science and Technology. The author has contributed to research in topics: Chemistry & Medicine. The author has an hindex of 2, co-authored 4 publications receiving 8 citations.

Coumarin–carbazole based functionalized pyrazolines: synthesis, characterization, anticancer investigation and molecular docking

Abstract: A series of novel pyrazoline scaffolds from coumarin–carbazole chalcones were synthesized. We explored various acetyl, amide, and phenyl substituents at the N-1 position of the pyrazoline core. The synthesized compounds were characterized by FTIR, 1H-NMR, 13C-NMR, DEPT, and mass spectroscopic techniques. The in vitro cytotoxicity study of all the synthesized compounds was evaluated against HeLa, NCI-H520 and NRK-52E cell lines. Compounds 4a and 7b became the most active compounds and exhibited their potential to arrest the cell cycle progression and induce apoptosis in both the cell lines. In addition, molecular docking studies revealed a higher binding affinity of both the molecules with CDK2 protein. Based on the obtained results, a comprehensive analysis is warranted to establish the role of compounds 4a and 7b as promising cancer therapeutic agents.

Design, synthesis, and characterization of novel substituted 1,2,4-oxadiazole and their biological broadcast

Abstract: In the current study, a novel combinatorial library of substituted 1,2,4-oxadiazoles bearing pyridine and thiazole have been synthesized via the condensation reaction of amidoxime and carboxylic acids and its derivatives in two way. The titled compounds were screened for their in vitro antimicrobial activity against three gram positive bacteria and three gram negative bacteria, In vitro antituberculosis activity against Mycobacterium tuberculosis H37RV and in vitro antimalarial activity against Plasmodium falciparum. Majority of the compounds were found to be active against gram positive bacteria. Compounds 6e, 6f, 7e, and 7f elaborate moderate antituberculosis activity against the first-line drug while 6c, 6d, 7c, and 7d intricate excellent antimalarial activity against Plasmodium falciparum strain.

Identification of RP-6685, an Orally Bioavailable Compound that Inhibits the DNA Polymerase Activity of Polθ.

Abstract: DNA polymerase theta (Polθ) is an attractive synthetic lethal target for drug discovery, predicted to be efficacious against breast and ovarian cancers harboring BRCA-mutant alleles. Here, we describe our hit-to-lead efforts in search of a selective inhibitor of human Polθ (encoded by POLQ). A high-throughput screening campaign of 350,000 compounds identified an 11 micromolar hit, giving rise to the N2-substituted fused pyrazolo series, which was validated by biophysical methods. Structure-based drug design efforts along with optimization of cellular potency and ADME ultimately led to the identification of RP-6685: a potent, selective, and orally bioavailable Polθ inhibitor that showed in vivo efficacy in an HCT116 BRCA2-/- mouse tumor xenograft model.

A Review of the Recent Development in the Synthesis and Biological Evaluations of Pyrazole Derivatives

Abstract: Pyrazoles are five-membered heterocyclic compounds that contain nitrogen. They are an important class of compounds for drug development; thus, they have attracted much attention. In the meantime, pyrazole derivatives have been synthesized as target structures and have demonstrated numerous biological activities such as antituberculosis, antimicrobial, antifungal, and anti-inflammatory. This review summarizes the results of published research on pyrazole derivatives synthesis and biological activities. The published research works on pyrazole derivatives synthesis and biological activities between January 2018 and December 2021 were retrieved from the Scopus database and reviewed accordingly.

Recent Applications of the Multicomponent Synthesis for Bioactive Pyrazole Derivatives

Abstract: Pyrazole and its derivatives are considered a privileged N-heterocycle with immense therapeutic potential. Over the last few decades, the pot, atom, and step economy (PASE) synthesis of pyrazole derivatives by multicomponent reactions (MCRs) has gained increasing popularity in pharmaceutical and medicinal chemistry. The present review summarizes the recent developments of multicomponent reactions for the synthesis of biologically active molecules containing the pyrazole moiety. Particularly, it covers the articles published from 2015 to date related to antibacterial, anticancer, antifungal, antioxidant, α-glucosidase and α-amylase inhibitory, anti-inflammatory, antimycobacterial, antimalarial, and miscellaneous activities of pyrazole derivatives obtained exclusively via an MCR. The reported analytical and activity data, plausible synthetic mechanisms, and molecular docking simulations are organized in concise tables, schemes, and figures to facilitate comparison and underscore the key points of this review. We hope that this review will be helpful in the quest for developing more biologically active molecules and marketed drugs containing the pyrazole moiety.

Coumarin–carbazole based functionalized pyrazolines: synthesis, characterization, anticancer investigation and molecular docking

Abstract: A series of novel pyrazoline scaffolds from coumarin–carbazole chalcones were synthesized. We explored various acetyl, amide, and phenyl substituents at the N-1 position of the pyrazoline core. The synthesized compounds were characterized by FTIR, 1H-NMR, 13C-NMR, DEPT, and mass spectroscopic techniques. The in vitro cytotoxicity study of all the synthesized compounds was evaluated against HeLa, NCI-H520 and NRK-52E cell lines. Compounds 4a and 7b became the most active compounds and exhibited their potential to arrest the cell cycle progression and induce apoptosis in both the cell lines. In addition, molecular docking studies revealed a higher binding affinity of both the molecules with CDK2 protein. Based on the obtained results, a comprehensive analysis is warranted to establish the role of compounds 4a and 7b as promising cancer therapeutic agents.

In vitro anti-TB properties, in silico target validation, molecular docking and dynamics studies of substituted 1,2,4-oxadiazole analogues against Mycobacterium tuberculosis.

Abstract: The alarming increase in multi- and extensively drug-resistant (MDR and XDR) strains of Mycobacterium tuberculosis (MTB) has triggered the scientific community to search for novel, effective, and safer therapeutics. To this end, a series of 3,5-disubstituted-1,2,4-oxadiazole derivatives (3a-3i) were tested against H37Rv, MDR and XDR strains of MTB. Of which, compound 3a with para-trifluorophenyl substituted oxadiazole showed excellent activity against the susceptible H37Rv and MDR-MTB strain with a MIC values of 8 and 16 µg/ml, respectively.To understand the mechanism of action of these compounds (3a-3i) and identify their putative drug target, molecular docking and dynamics studies were employed against a panel of 20 mycobacterial enzymes reported to be essential for mycobacterial growth and survival. These computational studies revealed polyketide synthase (Pks13) enzyme as the putative target. Moreover, in silico ADMET predictions showed satisfactory properties for these compounds, collectively, making them, particularly compound 3a, promising leads worthy of further optimisation.

A review of antimalarial activity of two or three nitrogen atoms containing heterocyclic compounds

Abstract: Malaria, a nocuous disease, which has become a major challenge for the health resulting in deaths of millions of people around the globe. Malaria is a parasitic disease propagated by mosquitoes and infects the human beings. Several species of Plasmodium are responsible for this life-threatening disease and Plasmodium falciparum being the most virulent. In order to eradicate the malarial parasite, the researchers are making consistent efforts in synthesizing new antimalarial drug candidates by paying attention to the various drug targets. In this manuscript, the main focus is on the antimalarial activity of numerous heterocyclic compounds reported by the researchers since 2010 against the different strains of Plasmodium. Antimalarial activities of the two and three nitrogen-containing heterocycles along with their structure–activity relationship are described.