更新于：2024-11-01

Falcipain 2

更新于：2024-11-01

基本信息

别名-

简介-

关联

100 项与 Falcipain 2 相关的临床结果

登录后查看更多信息

100 项与 Falcipain 2 相关的转化医学

登录后查看更多信息

0 项与 Falcipain 2 相关的专利（医药）

登录后查看更多信息

185

项与 Falcipain 2 相关的文献（医药）

2024-08-01·Bioorganic & Medicinal Chemistry Letters

Design, synthesis and molecular docking study of novel triazole–quinazolinone hybrids as antimalarial and antitubercular agents

Article

作者: Haval, Nitin B ; Choudhari, Prafulla B ; Kumari, Jyothi ; Rathod, Sanket S ; Bondle, Giribala M ; Mhetre, Udhav V ; Sriram, Dharmarajan ; Haval, Kishan P

In a quest to discover new antimalarial and antitubercular drugs, we have designed and synthesized a series of novel triazole-quinazolinone hybrids. The in vitro screening of the triazole-quinazolinone hybrid entities against the plasmodium species P. falciparum offered potent antimalarial molecules 6c, 6d, 6f, 6g, 6j & 6k owing comparable activity to the reference drugs. Furthermore, the target compounds were evaluated in vitro against Mycobacterium tuberculosis (MTB) H37Rv strain. Among the screened compounds, 6c, 6d and 6l were found to be the most active molecules with a MIC values of 19.57-40.68 μM. The cytotoxicity of the most active compounds was studied against RAW 264.7 cell line by MTT assay and no toxicity was observed. The computational study including drug likeness and ADMET profiling, DFT, and molecular docking study was done to explore the features of target molecules. The compounds 6a, 6g, and 6k exhibited highest binding affinity of -10.3 kcal/mol with docked molecular targets from M. tuberculosis. Molecular docking study indicates that all the molecules are binding to the falcipain 2 protease (PDB: 6SSZ) of the P. falciparum. Our findings indicated that these new triazole-quinazolinone hybrids may be considered hit molecules for further optimization studies.

2024-07-23·ACS Omega

Diversified Synthesis of N-Benzoyl Piperidine Tetraoxane Analogues Using Molybdenum Trioxide as a Newer Catalyst and Its Antiplasmodial Activity

Article

作者: Gupta, Rinkoo Devi ; Agarwal, Drishti ; Kumar, Arvind ; Awasthi, Satish Kumar ; Sharma, Bhawana

Molybdenum trioxide has been proven to be an efficient catalyst in synthesizing mixed N-benzoyl piperidine dispiro-1,2,4,5-tetraoxane analogues using a one-pot reaction. This catalyst facilitated the synthesis of 21 tetraoxanes using cyclic, acyclic, and aromatic ketones. The structure and methodology of this reaction have been validated by single-crystal X-ray analysis of compound ″3g″. The nature of dispiro-1,2,4,5-tetraoxane being synthesized has an impact on the overall yield of tetraoxanes such as symmetric dispiro-1,2,4,5-tetraoxanes ranging from 53 to 82%, while yields of N-benzoyl piperidine dispiro-1,2,4,5-tetraoxanes ranged from 26 to 51%. Additionally, the in vitro antiplasmodial activity of the newly developed tetraoxanes against Plasmodium falciparum was assessed, which exhibited significantly higher activity in the nanomolar range, with values ranging from 6.35 to 44.65 nM. Molecular docking studies revealed that newer tetraoxane derivatives bind to the active site of the falcipain-2 enzyme through H-bonding and hydrophobic contacts, which are the primary indicators of the effectiveness of the synthesized compounds. Findings suggest that these peculiar compounds may act as antiplasmodial agents, which spur further study and advancement in the battle against malaria.

2024-04-01·Molecular Diversity

In silico investigation of falcipain-2 inhibition by hybrid benzimidazole-thiosemicarbazone antiplasmodial agents: A molecular docking, molecular dynamics simulation, and kinetics study

Article

作者: Bine, Fritzgerald Kogge ; Hassan, Abrar Ul ; Tasheh, Stanley Numbonui ; Fouegue, Aymard Didier Tamafo ; Nkungli, Nyiang Kennet ; Ghogomu, Julius Numbonui

The emergence of artemisinin-resistant variants of Plasmodium falciparum necessitates the urgent search for novel antimalarial drugs. In this regard, an in silico study to screen antimalarial drug candidates from a series of benzimidazole-thiosemicarbazone hybrid molecules with interesting antiplasmodial properties and explore their falcipain-2 (FP2) inhibitory potentials has been undertaken herein. FP2 is a key cysteine protease that degrades hemoglobin in Plasmodium falciparum and is an important biomolecular target in the development of antimalarial drugs. Pharmacokinetic properties, ADMET profiles, MM/GBSA-based binding free energies, reaction mechanisms, and associated barrier heights have been investigated. DFT, molecular dynamics simulation, molecular docking, and ONIOM methods were used. From the results obtained, four ⁴N-substituted derivatives of the hybrid molecule (E)-2-(1-(5-chloro-1H-benzo[d]imidazol-2-yl)ethylidene)hydrazine-1-carbothioamide (1A) denoted 1B, 1C, 1D, and 1E are drug-like and promising inhibitors of FP2, exhibiting remarkably small inhibitory constants (5.94 × 10^-14 - 2.59 × 10^-04 __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__n M) and favorable binding free energies (-30.32 to -17.17 kcal/mol). Moreover, the ONIOM results have revealed that 1B and possibly 1C and 1D may act as covalent inhibitors of FP2. The rate-determining step of the thermodynamically favorable covalent binding mechanism occurs across a surmountable barrier height of 24.18 kcal/mol in water and 28.42 kcal/mol in diethyl ether. Our findings are useful for further experimental investigations on the antimalarial activities of the hybrid molecules studied.