It is widely reported that the overexpression of the C-C Motif Chemokine Receptor 2 (CCR2) has negative implications in neuroinflammatory diseases such as traumatic brain injury (TBI), although promising drugs to tackle this have been less forthcoming. As of 2016, only 2 drugs specifically targeting this receptor have made their way to market, with unsuccessful outcome unfortunately, suggesting that the search for more specific and precise ligands is utterly necessary. In this paper we hypothesized that by targeting Glu291, Met295, Trp98, Leu45 and Val189 amino acids, essential in the binding of CCR2 with C-C Motif Chemokine Ligand 2 (CCL2), the endogenous substrate, mitigates its activity in TBI. We used a pharmacophore model to screen for suitable ligands that may bind to CCR2, which returned 871 ligands. Docking and molecular dynamics results uncovered that two ligands (A102) and (A435) contained several of those important residues and showed a stability and compactness when in complex with CCR2, with these results confirmed by MMGBSA calculations with A102 recording a better interaction compared to A435. Finally, a PPI network was built to explore downstream signaling being regulated by both ligands in TBI, showing amyloid precursor protein (APP) as a key target and neuroactive-ligand receptor interaction (1.80E-27) the top functional annotated category. In conclusion, for the first time we report novel ligands A102 and A435 targeting CCR2 as a potential new pharmacological approach to target inflammation post-TBI.

01 Aug 2020·Plant DiseaseQ2 · AGRICULTURAL & FORESTRY SCIENCE

Antagonistic Activity of Endophytic and Rhizosphere Fungi Isolated From Sea Purslane (Sesuvium portulacastrum) Against Pythium Damping off of Cucumber

Q2 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Al-Sadi, Abdullah M. ; Velazhahan, Rethinasamy ; Maharachchikumbura, S. S. N. ; Karunasinghe, Thamodini G.

This study was conducted to investigate the antagonistic activity of endophytic and rhizosphere fungi isolated from a medicinal plant, Sesuvium portulacastrum, against Pythium aphanidermatum, the cause of damping off of cucumber. A total of 40 endophytic and 19 rhizosphere fungi were isolated from S. portulacastrum. Three endophytic isolates and two rhizosphere isolates gave >50% suppression of P. aphanidermatum in the in vitro dual-culture tests. Scanning electron microscopic studies at the inhibition zone showed hyphae wall damage and abnormal mycelial growth of the genus Pythium. Molecular analysis identified the antagonistic endophytes as Aspergillus insulicola (isolate A435), A. insulicola (A419), and Aspergillus melleus (A412) and the rhizosphere antagonists as Aspergillus terreus (A213) and Aspergillus luchuensis (A116). Except for A116, the culture filtrates of the other antagonists significantly increased the electrolyte leakage from Pythium mycelia, whereas ethyl acetate extracts of A435, A412, and A213 showed significant growth suppression. All five antagonists were able to produce varying amounts of cellulase and β-glucanase enzymes. However, A435, A412, and A213 showed significantly higher cellulase activity, whereas A435 and A116 showed the highest β-glucanase activity. Controlled glasshouse growth experiments showed that isolates A435 and A116 resulted in up to 70% control of damping off, whereas isolates A412 and A213 showed 30 to 40% damping-off control. The antagonists A435, A116, and A213 also contributed to increased cucumber shoot length as well as shoot and root dry mass. The synergetic effects of metabolites and hydrolytic enzymes could be the reason for the variation between isolates in the antagonistic activity and cucumber growth promotion. This study reports for the first time A. insulicola, A. melleus, and A. luchuensis as potential biocontrol agents against P. aphanidermatum-induced damping off of cucumber.

01 Oct 1970·Indian journal of experimental biology

A-435-a new antifungal agent.

Article

Author: Pal, A ; Nandi, P

100 Deals associated with A-435

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	US	KLUS Pharma, Inc.Startup	15 Aug 2023

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