Novel Pyran-Linked Phthalazinone-Pyrazole Hybrids: Synthesis, Cytotoxicity Evaluation, Molecular Modeling, and Descriptor Studies.

Frontiers in Chemistry
M Shaheer MalikSaleh A Ahmed

Abstract

A series of novel pyran-linked phthalazinone-pyrazole hybrids were designed and synthesized by a facile one-pot three-component reaction employing substituted phthalazinone, 1H-pyrazole-5-carbaldehyde, and active methylene compounds. Optimization studies led to the identification of L-proline and ethanol as efficient catalyst and solvent, respectively. This was followed by evaluation of anticancer activity against solid tumor cell lines of lung and cervical carcinoma that displayed IC50 values in the range of 9.8-41.6 µM. Molecular modeling studies were performed, and crucial interactions with the target protein were identified. The drug likeliness nature of the compounds and molecular descriptors such as molecular flexibility, complexity, and shape index were also calculated to understand the potential of the synthesized molecules to act as lead-like molecule upon further detailed biological investigations as well as 3D-QSAR studies.

References

Feb 1, 1995·Protein Engineering·A C WallaceJ M Thornton
Jul 1, 1994·Journal of Clinical Pharmacology·P B InskeepN Gerber
Jun 10, 2004·Bioorganic & Medicinal Chemistry·Jin Sung KimChong-Ock Lee
Mar 10, 2005·The Annals of Pharmacotherapy·Steven Thomas Boyd, Brad Allen Fremming
Apr 20, 2005·Bioorganic & Medicinal Chemistry Letters·Vincent M LohAlan J Whittle
Jun 26, 2008·Chemistry : a European Journal·Nicolas Isambert, Rodolfo Lavilla
Jan 20, 2009·Current Medicinal Chemistry·S Prasanna, R J Doerksen
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Oct 16, 2009·Journal of Medicinal Chemistry·Frank LoveringChristine Humblet
Mar 23, 2012·Chemical Reviews·Alexander DömlingKan Wang
Dec 1, 2004·Drug Discovery Today. Technologies·Christopher A Lipinski
Jul 18, 2014·Chemical Reviews·Benjamin H RotsteinAndrei K Yudin
Dec 9, 2014·European Journal of Medicinal Chemistry·Noemí VilaCarmen Terán
Mar 12, 2015·Future Oncology·Camille C Gunderson, Kathleen N Moore
May 19, 2016·European Journal of Medicinal Chemistry·Mohemmed Faraz KhanMohammad Shaquiquzzaman
Aug 31, 2016·Drug Discovery Today·Oscar Méndez-Lucio, José L Medina-Franco
Dec 28, 2016·Journal of Chemical Information and Modeling·Jerome G P Wicker, Richard I Cooper
Jan 13, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Khalid KarrouchiM'hammed Ansar
Mar 7, 2019·International Journal of Impotence Research·Pramod KrishnappaJuan Ignacio Martinez-Salamanca
Jul 25, 2019·Expert Opinion on Pharmacotherapy·Marco Krasselt, Christoph Baerwald
Aug 12, 2019·Bioorganic & Medicinal Chemistry·Jaiprakash SangshettiDevanand B Shinde
Jun 11, 2020·Cancer Metastasis Reviews·Shailesh Kumar ThakurJaytrilok Choudhary
Sep 10, 2020·PloS One·Jiefei TongMichael F Moran
Apr 6, 2021·International Journal of Cancer. Journal International Du Cancer·Jacques FerlayFreddie Bray

❮ Previous
Next ❯

Software Mentioned

LIGPLOT
Chem3D ultra
PyMol
ChemDraw ultra
Molinspiration
OSIRIS property explorer
AutoDockTools
SwissADME
DataWarrior
MOPAC

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.