Structural based investigation of novel pyrazole-thiazole Hybrids as dual CDK-1 and CDK-2 inhibitors for cancer chemotherapy

Obakachi, Vincent A.; Idowu, Kehinde; Kushwaha, Narva Deshwar; Akinpelu, Olayinka I.; Kushwaha, Babita; Merugu, Srinivas Reddy; Kayamba, Francis; Kumalo, Hezekiel M.; Karpoormath, Rajshekhar

doi:10.1080/08927022.2022.2045016

Cited by 6 publications

(4 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Utilizing BIOVIA Discovery Studio 2021 (DSV) client software, geometry optimization was carried out to convert the previously created 2‐dimensional scaffold configurations to 3‐dimensional coordinates [31] . Furthermore, the energy of all analogs was minimized with the addition of non‐polar hydrogen atoms, and with the formation of rotatable bonds [32] …”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

In Silico Design and Investigation of Novel Thiazetidine Derivatives as Potent Inhibitors of PrpR in Mycobacterium tuberculosis

Dasmahapatra

Rajasekhar²,

Neelima³

et al. 2022

Chemistry & Biodiversity

View full text Add to dashboard Cite

Tuberculosis is one of the most life‐threatening acute infectious diseases diagnosed in humans. In the present investigation, a series of 16 new disubstituted 1,3‐thiazetidines derivatives is designed, and investigated via various in silico methods for their potential as anti‐tubercular agent by evaluating their ability to block the active site of PrpR transcription factor protein of Mycobacterium tuberculosis. The efficacy of the molecules was initially assessed with the help of AutoDock Vina algorithm. Further Glide module is used to redock the previously docked complexes. The binding energies and other physiochemical properties of the designed molecules were evaluated using the Prime‐MM/GBSA and the QikProp module, respectively. The results of docking revealed the nature, site of interaction and the binding affinity between the proposed candidates and the active site of PrpR. Further the inhibitory effect of the scaffolds was predicted and evaluated employing a machine learning‐based algorithm and was used accordingly. Further, the molecular dynamics simulation studies ascertained the binding characteristics of the unique 13, when analysed across a time frame of 100 ns with GROMACS software. The results show that the proposed 1,3‐thiazetidine derivatives such as 10, 11, 13 and 14 could be potent and selective anti‐tubercular agents as compared to the standard drug Pyrazinamide. Finally, this study concludes that designed thiazetidines can be employed as anti‐tubercular agents. Undeniably, the results may guide the experimental biologists to develop safe and non‐toxic drugs against tuberculosis by demanding further in vivo and in vitro analyses.

show abstract

Section: Methodsmentioning

confidence: 99%

“…[31] Furthermore, the energy of all analogs was minimized with the addition of non-polar hydrogen atoms, and with the formation of rotatable bonds. [32]…”

Section: Compilation Of Datasetmentioning

confidence: 99%

In Silico Design and Investigation of Novel Thiazetidine Derivatives as Potent Inhibitors of PrpR in Mycobacterium tuberculosis

Dasmahapatra

Rajasekhar²,

Neelima³

et al. 2022

Chemistry & Biodiversity

View full text Add to dashboard Cite

show abstract

“…CDK-2 and CCNB1 are two key molecules involved in cell cycle regulation, and they have been explored as potential anti-cancer targets due to their critical roles in controlling cell division. Targeting these molecules can disrupt the uncontrolled proliferation of cancer cells, making them attractive candidates for cancer therapy [23,24].…”

Section: Introductionmentioning

confidence: 99%

An Integrated Molecular Networking and Docking Approach to Characterize the Metabolome of Helichrysum splendidum and Its Pharmaceutical Potentials

Lephatsi,

Choene,

Kappo

et al. 2023

Metabolites

View full text Add to dashboard Cite

South Africa is rich in diverse medicinal plants, and it is reported to have over 35% of the global Helichrysum species, many of which are utilized in traditional medicine. Various phytochemical studies have offered valuable insights into the chemistry of Helichrysum plants, hinting at bioactive components that define the medicinal properties of the plant. However, there are still knowledge gaps regarding the size and diversity of the Helichrysum chemical space. As such, continuous efforts are needed to comprehensively characterize the phytochemistry of Helichrysum, which will subsequently contribute to the discovery and exploration of Helichrysum-derived natural products for drug discovery. Thus, reported herein is a computational metabolomics work to comprehensively characterize the metabolic landscape of the medicinal herb Helichrysum splendidum, which is less studied. Metabolites were methanol-extracted and analyzed on a liquid chromatography–tandem mass spectrometry (LC-MS/MS) system. Spectral data were mined using molecular networking (MN) strategies. The results revealed that the metabolic map of H. splendidum is chemically diverse, with chemical superclasses that include organic polymers, benzenoids, lipid and lipid-like molecules, alkaloids, and derivatives, phenylpropanoids and polyketides. These results point to a vastly rich chemistry with potential bioactivities, and the latter was demonstrated through computationally assessing the binding of selected metabolites with CDK-2 and CCNB1 anti-cancer targets. Molecular docking results showed that flavonoids (luteolin, dihydroquercetin, and isorhamnetin) and terpenoids (tiliroside and silybin) interact strongly with the CDK-2 and CCNB1 targets. Thus, this work suggests that these flavonoid and terpenoid compounds from H. splendidum are potentially anti-cancer agents through their ability to interact with these proteins involved in cancer pathways and progression. As such, these actionable insights are a necessary step for further exploration and translational studies for H. splendidum-derived compounds for drug discovery.

show abstract

“…In the drug designing process, molecular docking can be used as a tool to identify the structural requirement for efficient protein-ligand binding, virtual screening, drug repositioning, identification of the compounds that can target more than one protein of the same disease and prediction of drug off-target activity, and many more (Pinzi and Rastelli, 2019). Ample studies are reported that have implemented the use of molecular docking and/or hybrid with experimental studies to search for various anticancer (Lone et al, 2017;Tutone and Almerico, 2017;Bhattacharya et al, 2022;El-Sayed et al, 2022a, 2022cGhosh et al, 2022;Khanam et al, 2022;Obakachi et al, 2022), antimalarial (Manhas et al, 2016(Manhas et al, , 2018(Manhas et al, , 2019a(Manhas et al, , 2019bBenjamin et al, 2022), antitubercular (Lone et al, 2018;Akki et al, 2022;Kaur and Singh, 2022;Modi et al, 2022;Sanka et al, 2022), etc., molecules. This depicts the importance of docking in the field of rational drug design.…”

Section: Introductionmentioning

confidence: 99%

A comprehensive analysis of the role of molecular docking in the development of anticancer agents against the cell cycle CDK enzyme

SOLANKI¹,

RANA²,

Jha³

et al. 2023

Biocell

View full text Add to dashboard Cite

Cancer is considered one of the most lethal diseases responsible for causing deaths worldwide. Although there have been many breakthroughs in anticancer development, cancer remains the major cause of death globally. In this regard, targeting cancer-causing enzymes is one of the efficient therapeutic strategies. Biological functions like cell cycle, transcription, metabolism, apoptosis, and other depend primarily on cyclin-dependent kinases (CDKs). These enzymes help in the replication of DNA in the normal cell cycle process, and deregulation in the functioning of any CDK can cause abnormal cell growth, which leads to cancer. This review is focused on anticancer drug discovery against cell cycle CDK enzyme using an in silico technique, i.e., molecular docking studies. Molecular docking helps in deciphering the key interactions formed within the inhibitor and the respective enzyme. This concise study provides an overview of the most current in silico research advancements made in the field of anticancer drug discovery. The findings presented in the current review article can help in understanding the nature of inhibitor-target interactions and provide information on the structural and molecular prerequisites for the inhibition of cell cycle CDKs.

show abstract

Structural based investigation of novel pyrazole-thiazole Hybrids as dual CDK-1 and CDK-2 inhibitors for cancer chemotherapy

Cited by 6 publications

References 58 publications

In Silico Design and Investigation of Novel Thiazetidine Derivatives as Potent Inhibitors of PrpR in Mycobacterium tuberculosis

In Silico Design and Investigation of Novel Thiazetidine Derivatives as Potent Inhibitors of PrpR in Mycobacterium tuberculosis

An Integrated Molecular Networking and Docking Approach to Characterize the Metabolome of Helichrysum splendidum and Its Pharmaceutical Potentials

A comprehensive analysis of the role of molecular docking in the development of anticancer agents against the cell cycle CDK enzyme

Contact Info

Product

Resources

About