Home Blog of Signal Transduction Transmembrane Transporters Calcium Channel Design, synthesis and anti-Chikungunya virus activity of lomerizine derivatives

Category

Archives

Popular Post

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Design, synthesis and anti-Chikungunya virus activity of lomerizine derivatives

Chikungunya fever is an acute infectious disease caused by Chikungunya virus (CHIKV) and transmitted by Aedes mosquito. It is characterized by fever, rash and arthralgia with no effective drugs. Lomerizine (Lom) is a new generation calcium antagonist, which is mainly used in the treatment of migraine. Certain antiviral function of Lom was shown by some research. In our study, a series of new derivatives of Lom were designed and synthesized, and their in-vitro anti-CHIKV activity was tested. The results showed that Lom and its derivatives had potent anti-CHIKV activity and low cytotoxicity. Among them, compounds B1 and B7 showed most potent antiviral activity. Besides, structure-activity relationships, in-silico ADMET properties were also analyzed. Molecular docking study was performed to rationalize the SAR and analyze the possible binding modes between B1 and amino acid residues in the active site of nsP3 protein to enhance the understanding of their action as antiviral agents. These finding provides research basis for the design and synthesis of effective anti-CHIKV drugs with Lom as the lead compound.

 

Comments:

That sounds like an interesting study! Chikungunya fever is indeed an acute infectious disease caused by the Chikungunya virus (CHIKV) and transmitted by the Aedes mosquito. The symptoms typically include fever, rash, and arthralgia (joint pain), and currently, there are no effective drugs specifically approved for treating Chikungunya fever.

Lomerizine (Lom), a new generation calcium antagonist primarily used in the treatment of migraines, has shown some antiviral properties in previous research. In your study, a series of new derivatives of Lom were designed and synthesized, and their in-vitro anti-CHIKV activity was tested. The results demonstrated that both Lom and its derivatives exhibited potent anti-CHIKV activity while maintaining low cytotoxicity. Specifically, compounds B1 and B7 displayed the most potent antiviral activity among the derivatives.

In addition to evaluating the antiviral activity, you also analyzed the structure-activity relationships and in-silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of the Lom derivatives. Furthermore, a molecular docking study was conducted to explain the structure-activity relationships and explore the possible binding modes between compound B1 and the amino acid residues in the active site of the nsP3 protein. This analysis aimed to enhance the understanding of how these compounds function as antiviral agents.

Overall, your findings provide a research foundation for the design and synthesis of effective anti-CHIKV drugs, with Lom serving as the lead compound. Further development and optimization of these Lom derivatives may lead to the discovery of novel treatments for Chikungunya fever.

Related Products

Cat.No. Product Name Information
S4084 Lomerizine 2HCl Lomerizine dihydrochloride (KB-2796) is a relatively new L- and T-type calcium channel blocker used in the treatment of migraine.

Related Targets

Calcium Channel