title: Protease inhibitors from marine actinobacteria as a potential source for antimalarial compound.
abstract: The study was planned to screen the marine actinobacterial extract for the protease inhibitor activity and its anti- Pf activity under in vitro and in vivo conditions. Out of 100 isolates, only 3 isolates exhibited moderate to high protease inhibitor activities on trypsin, chymotrypsin and proteinase K. Based on protease inhibitor activity 3 isolates were chosen for further studies. The potential isolate was characterized by polyphasic approach and identified as Streptomyces sp LK3 (JF710608). The lead compound was identified as peptide from Streptomyces sp LK3. The double-reciprocal plot displayed inhibition mode is non-competitive and it confirms the irreversible nature of protease inhibitor. The peptide from Streptomyces sp LK3 extract showed significant anti plasmodial activity (IC50: 25.78 µg/ml). In in vivo model, the highest level of parasitemia suppression (≈ 45%) was observed in 600 mg/kg of the peptide. These analyses revealed no significant changes were observed in the spleen and liver tissue during 8 dpi. The results confirmed up-regulation of TGF-β and down regulation of TNF-α in tissue and serum level in PbA infected peptide treated mice compared to PbA infection. The results obtained infer that the peptide possesses anti- Pf activity activity. It suggests that the extracts have novel metabolites and could be considered as a potential source for drug development.
authors.affiliation: Environmental Biotechnology Division, School of Bio Sciences and Technology, VIT University, Vellore, Tamil nadu, India.
authors.forename: L
authors.initials: L
authors.lastname: Karthik
authors.affiliation: Environmental Biotechnology Division, School of Bio Sciences and Technology, VIT University, Vellore, Tamil nadu, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kumar
authors.affiliation: Immunology Lab, Department of Zoology, University of Calcutta, Kolkata, West Bengal, India.
authors.forename: Tarun
authors.initials: T
authors.lastname: Keswani
authors.affiliation: Immunology Lab, Department of Zoology, University of Calcutta, Kolkata, West Bengal, India.
authors.forename: Arindam
authors.initials: A
authors.lastname: Bhattacharyya
authors.affiliation: Genetics Division, School of Bio Sciences and Technology, VIT University, Vellore, Tamil nadu, India.
authors.forename: S Sarath
authors.initials: SS
authors.lastname: Chandar
authors.affiliation: Environmental Biotechnology Division, School of Bio Sciences and Technology, VIT University, Vellore, Tamil nadu, India.
authors.forename: K V
authors.initials: KV
authors.lastname: Bhaskara Rao
mesh_terms: D039903:Actinobacteria / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D059001:Aquatic Organisms / Q000737:chemistry* / Q000378:metabolism; D001482:Base Composition; D002918:Chymotrypsin / Q000037:antagonists & inhibitors / Q000378:metabolism; D016000:Cluster Analysis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D020128:Inhibitory Concentration 50; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D008297:Male; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D011480:Protease Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011487:Protein Conformation; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000235:genetics; D012623:Seawater / Q000382:microbiology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014357:Trypsin / Q000378:metabolism
chemical_list: D000962:Antimalarials; D011480:Protease Inhibitors; D012336:RNA, Ribosomal, 16S; D002918:Chymotrypsin; D014357:Trypsin