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Identification of novel thiourea‐stilbene‐triazine conjugates as persuasive lymphoid tyrosine phosphatase inhibitors
Author(s) -
Batool Iram,
Jabeen Farukh,
Vellore Nadeem Ahmed,
Shabir Ghulam,
Saeed Aamer
Publication year - 2020
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.4060
Subject(s) - chemistry , thiourea , triazine , protein tyrosine phosphatase , docking (animal) , stereochemistry , substituent , conjugate , tyrosine , combinatorial chemistry , biochemistry , organic chemistry , mathematical analysis , mathematics , medicine , nursing
A library of novel thiourea‐based symmetrical stilbene‐triazines ( 5a‐i ) was synthesized in an effort to develop new protein tyrosine phosphatase LYP inhibitors. The versatile nature of 2,4,6‐trichloro‐1,3,5‐triazine allows considerable scope for derivatization and hence exploration of structure activity relationships. A convenient and versatile three‐step synthetic approach involved the successive replacement of the two chloro groups of 2,4,6‐trichloro‐1,3,5‐triazine by a variety of substituents for structural modification. The newly synthesized derivatives were subjected to tyrosine phosphatase LYP inhibition studies. The results for the in vitro bioassays were promising with the identification of compound 5k and 5l having a 4‐methyl and 4‐methoxy substituent on phenyl ring, as the lead and selective candidate for LYP inhibition with an IC 50 value of 2.1 ± 0.05 μM and 28 ± 3.3 μM, respectively. Moreover, docking studies were carried out to determine the possible interaction sites of thiourea‐based stilbene‐triazine compounds with Lymphoid Tyrosine Phosphatase. Results of docking computations further ascertained the inhibitory potential of compound 5k and 5l . The results indicated that the compound 5k may serve as a structural model for the design of most potent LYP inhibitors.