ABSTRACT
A transition-metal- and oxidant-free DNP (2,4-dinitrophenol)-catalyzed atom-economical regio- and diastereoselective synthesis of monofunctionalized α-alkynyl-3-amino-2-oxindole derivatives by C-H bond functionalization of cyclic amines and alkynes with indoline-2,3-diones has been developed. This cascade event sequentially involves the reductive amination of indoline-2,3-dione by imine formation and cross coupling between C(sp(3) )-H and C(sp)-H of the cyclic amines and alkynes. This reaction offers an efficient and attractive pathway to different types of α-alkynyl-3-amino-2-oxindole derivatives in good yields with a wide tolerance of functional groups. The salient feature of this methodology is that it completely suppresses the homocoupling of alkynes. To the best of our knowledge, this is the first example of a DNP-catalyzed metal-free direct C(sp(3) )-H and C(sp)-H bond functionalization providing biologically active α-alkynyl-3-amino-2-oxindole scaffolds.
ABSTRACT
Synthesis of new chiral thiourea derivatives (27 examples) as anticancer agents has been described. Three compound 7d (NSC code 761448/1), 7e1 (NSC code 767161/1), and 7e3 (NSC code 767160/1) were found to exhibit higher anticancer activity than 5-fluorouracil against Colon cancer, Melanoma, Ovarian cancer, and Breast cancer subpanels. The effect of stereochemistry of amino acid residues on the tumor growth inhibitory activity has also been studied.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Colonic Neoplasms/drug therapy , Thiourea/analogs & derivatives , Thiourea/pharmacology , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Colonic Neoplasms/pathology , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Conformation , Stereoisomerism , Structure-Activity Relationship , Thiourea/chemical synthesis , Thiourea/chemistryABSTRACT
Novel bisstyryl derivatives of bakuchiol using Heck coupling reaction as the key step were synthesized and screened against a panel of six oral cavity pathogens for their antimicrobial activity. Four compounds (9-12) showed two to fourfold and four to eightfold better activity (MIC 0.25-16 microg/ml) than bakuchiol and triclosan respectively. These compounds effectively inhibit the biofilm formation of single and multiple species at 2 - 8 x MICs. 4- and 4'-Hydroxy/methoxy styryl moieties of the bakuchiol derivatives play a pivotal role towards the activity as established in the SAR studies. Mechanism of action studies revealed microbial membrane structure disruption as the probable mode of action of these compounds.
