scholarly journals Quinoline-triazole hybrids inhibit falcipain-2 and arrest the development of Plasmodium falciparum at the trophozoite stage

RSC Advances ◽  
2019 ◽  
Vol 9 (67) ◽  
pp. 39410-39421
Author(s):  
Anju Singh ◽  
Md Kalamuddin ◽  
Asif Mohmmed ◽  
Pawan Malhotra ◽  
Nasimul Hoda
Keyword(s):  
Plasmodium Falciparum ◽  
Protease Inhibitors ◽  
Cysteine Protease ◽  
Cysteine Protease Inhibitors ◽  
Trophozoite Stage

The present study involves development of novel quinoline triazole-containing cysteine protease inhibitors which arrest the development of P. falciparum at the trophozoite stage.

scholarly journals Comparison of Efficacies of Cysteine Protease Inhibitors against Five Strains of Plasmodium falciparum

2001 ◽  
Vol 45 (3) ◽  
pp. 949-951 ◽  
Author(s):  
Ajay Singh ◽  
Philip J. Rosenthal
Keyword(s):  
Plasmodium Falciparum ◽  
Protease Inhibitors ◽  
Cysteine Protease ◽  
Antimalarial Drug ◽  
Drug Target ◽  
Antimalarial Drugs ◽  
Cross Resistance ◽  
Cysteine Protease Inhibitors ◽  
Antimalarial Agents ◽  
Parasite Strains

ABSTRACT Falcipain-2, a cysteine protease and essential hemoglobinase ofPlasmodium falciparum, is a potential antimalarial drug target. We compared the falcipain-2 sequences and sensitivities to cysteine protease inhibitors of five parasite strains that differ markedly in sensitivity to established antimalarial drugs. The sequence of falcipain-2 was highly conserved, and the sensitivities of all of the strains to falcipain-2 inhibitors were very similar. Thus, cross-resistance between cysteine protease inhibitors and other antimalarial agents is not expected in parasites that are now circulating and falcipain-2 remains a promising chemotherapeutic target.

Expression and characterization of the Plasmodium falciparum haemoglobinase falcipain-3

2001 ◽  
Vol 360 (2) ◽  
pp. 481-489 ◽  
Author(s):  
Puran S. SIJWALI ◽  
Bhaskar R. SHENAI ◽  
Jiri GUT ◽  
Ajay SINGH ◽  
Philip J. ROSENTHAL
Keyword(s):  
Plasmodium Falciparum ◽  
Protease Inhibitors ◽  
Cysteine Protease ◽  
Active Form ◽  
Cysteine Proteases ◽  
Food Vacuole ◽  
Acidic Ph ◽  
Cysteine Protease Inhibitors ◽  
Peptide Substrates ◽  
Hydrolysis Of

In the malaria parasite Plasmodium falciparum, erythrocytic trophozoites hydrolyse haemoglobin to provide amino acids for parasite protein synthesis. Cysteine protease inhibitors block parasite haemoglobin hydrolysis and development, indicating that cysteine proteases are required for these processes. Three papain-family cysteine protease sequences have been identified in the P. falciparum genome, but the specific roles of their gene products and other plasmodial proteases in haemoglobin hydrolysis are uncertain. Falcipain-2 was recently identified as a principal trophozoite cysteine protease and potential drug target. The present study characterizes the related P. falciparum cysteine protease falcipain-3. As is the case with falcipain-2, falcipain-3 is expressed by trophozoites and appears to be located within the food vacuole, the site of haemoglobin hydrolysis. Both proteases require a reducing environment and acidic pH for optimal activity, and both prefer peptide substrates with leucine at the P2 position. The proteases differ, however, in that falcipain-3 undergoes efficient processing to an active form only at acidic pH, is more active and stable at acidic pH, and has much lower specific activity against typical papain-family peptide substrates, but has greater activity against native haemoglobin. Thus falcipain-3 is a second P. falciparum haemoglobinase that is particularly suited for the hydrolysis of native haemoglobin in the acidic food vacuole. The redundancy of cysteine proteases may offer optimized hydrolysis of both native haemoglobin and globin peptides. Consideration of both proteases will be necessary to evaluate cysteine protease inhibitors as antimalarial drugs.

Evaluation of a microassay for human kininogens as cysteine protease inhibitors

1991 ◽  
Vol 26 (2) ◽  
pp. 113-124 ◽  
Author(s):  
Tove S. Karlsrud ◽  
Ansgar O. Aasen ◽  
Harald T. Johansen
Keyword(s):  
Protease Inhibitors ◽  
Cysteine Protease ◽  
Cysteine Protease Inhibitors

The 1,4-naphthoquinone scaffold in the design of cysteine protease inhibitors

2007 ◽  
Vol 15 (15) ◽  
pp. 5340-5350 ◽  
Author(s):  
Cláudia Valente ◽  
Rui Moreira ◽  
Rita C. Guedes ◽  
Jim Iley ◽  
Mohammed Jaffar ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Cysteine Protease ◽  
Cysteine Protease Inhibitors

scholarly journals Design, Synthesis, Evaluation and Thermodynamics of 1-Substituted Pyridylimidazo[1,5-a]Pyridine Derivatives as Cysteine Protease Inhibitors

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e69982 ◽  
Author(s):  
Mohd Sajid Khan ◽  
Mohd Hassan Baig ◽  
Saheem Ahmad ◽  
Shapi Ahmad Siddiqui ◽  
Ashwini Kumar Srivastava ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Cysteine Protease ◽  
Pyridine Derivatives ◽  
Cysteine Protease Inhibitors ◽  
Design Synthesis

ChemInform Abstract: Synthesis of Macrocyclic Trypanosomal Cysteine Protease Inhibitors.

ChemInform ◽  
2009 ◽  
Vol 40 (14) ◽  
Author(s):  
Yen Ting Chen ◽  
Ricardo Lira ◽  
Elizabeth Hansell ◽  
James H. McKerrow ◽  
William R. Roush
Keyword(s):  
Protease Inhibitors ◽  
Cysteine Protease ◽  
Cysteine Protease Inhibitors

A comparative study of warheads for design of cysteine protease inhibitors

2017 ◽  
Vol 27 (22) ◽  
pp. 5031-5035 ◽  
Author(s):  
Daniel G. Silva ◽  
Jean F.R. Ribeiro ◽  
Daniela De Vita ◽  
Lorenzo Cianni ◽  
Caio Haddad Franco ◽  
...  
Keyword(s):  
Comparative Study ◽  
Protease Inhibitors ◽  
Cysteine Protease ◽  
Cysteine Protease Inhibitors
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