Synthesis and Evaluation of Isatin Schiff Bases Against Plant Pathogens Validated Through Aspartyl Protease and Acetylcholine Binding Proteins Docked Studies

: Schiff bases of isatin were synthesized by reacting isatin with substituted aromatic amines and were characterized by UV-Visible, 1HNMR, 13CNMR, IR, and microanalytical data. All the synthesized isatin Schiff bases were screened in vitro against wheat pathogenic fungi Bipolaris sorokiniana, Alternaria triticina using spore inhibition technique and brinjal parasite- Meloidogyne incognita by egg hatch inhibition and J2 mortality. The in vitro study and docking simulation studies revealed that the 3-(2,4,5-trichlorophenylimino)indolin-2-one 6f and 3-(2,4-dinitrophenylimino)indolin-2-one 6c substituted with tri-halogen and dinitro electron-withdrawing groups were found to be promising antipathogenic candidates. The possible binding interactions of tested compounds with Aspartyl protease and Acetylcholine binding proteins were analyzed through molecular docking.

Novel Three-Finger Neurotoxins from Naja melanoleuca Cobra Venom Interact with GABAA and Nicotinic Acetylcholine Receptors

Cobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABAA receptors (GABAARs) with different efficacy, an important role of the TFTs central loop in binding to these receptors being demonstrated. We supposed that the positive charge (Arg36) in this loop of α-cobratoxin may explain its high affinity to GABAAR and here studied α-neurotoxins from African cobra N. melanoleuca venom for their ability to interact with GABAARs and nAChRs. Three α-neurotoxins, close homologues of the known N. melanoleuca long neurotoxins 1 and 2, were isolated and sequenced. Their analysis on Torpedocalifornica and α7 nAChRs, as well as on acetylcholine binding proteins and on several subtypes of GABAARs, showed that all toxins interacted with the GABAAR much weaker than with the nAChR: one neurotoxin was almost as active as α-cobratoxin, while others manifested lower activity. The earlier hypothesis about the essential role of Arg36 as the determinant of high affinity to GABAAR was not confirmed, but the results obtained suggest that the toxin loop III may contribute to the efficient interaction of some long-chain neurotoxins with GABAAR. One of isolated toxins manifested different affinity to two binding sites on Torpedo nAChR.