Recent Updates on Indole Derivatives as Kinase Inhibitors in the Treatment of Cancer

Abstract

Cancer is becoming a global threat as its treatment accounts for many challenges. Hence, newer inventions prioritize the requirement of developing novel anticancer agents. In this context, kinases have been exclusively investigated and developed as a promising and novel class of drug targets for anticancer regimen. Indole derivatives have been found to be most effective for targeting multiple kinases, such as PIM, CDK, TK, AKT, SRC, PI3K, PKD, GSK, etc., to inhibit cell proliferation for cancer. Recently, a group of researchers have proposed their research outcomes related to this moiety, such as Zhang et al. described some potent PI3K inhibitors by substitution at the 4th position of the indole ring. Kassis et al. enumerated several potent CDK5 inhibitors by substituting the 2nd and 6th positions of the indole ring. In the present review, we have taken the initiative to summarize structure-activity relationship (SAR) studies of indole derivatives as kinase inhibitors for the development of potential inhibitors.

N-Derivatives of (Z)-Methyl 3-(4-Oxo-2-thioxothiazolidin-5-ylidene)methyl)-1H-indole-2-carboxylates as Antimicrobial Agents—In Silico and In Vitro Evaluation

“…All compounds have been assessed for their ADMET profile in ADMET Predictor version 10.4 provided by the Simulation Plus software package [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ...…”

“…Another promising scaffold is the indole ring attracting considerable attention because of its presence in proteins, amino acids, and bioactive alkaloids [ 19 ], and the wide range of biological activities of its derivatives [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ], among which is antimicrobial activity [ 36 , 37 , 38 , 39 , 40 , 41 ]. Furthermore, indole ring is present in many approved drugs ( Figure 2 ).…”

Ruthenium-Catalyzed Oxidative Synthesis of N-(2-triazine)indoles by C-H Activation

“…We commenced our studies by identifying the reaction of N 2 ,N 2 -dimethyl-N 4 -phenyl-1,3,5-triazine-2,4-diamine (1a) with 1,2-diphenylethyne (2a) in the presence of a ruthenium catalyst. We focused our optimization studies on a variety of additives (Cu(OAc) 2 , Cu (NO 3 ) 2 , Cu (NO 3 ) 2 , CuBr 2 , Cu(CF 3 SO 3 ) 2 , NaOAc, CsOAc); the initial screening indicated that the use of Cu(OAc) 2 proved to be optimal and gave a higher yield ( Table 1, entries 1-7).…”

“…Indoles are one of the most important nitrogen heterocycles in medicinal chemistry, natural products, and organic synthesis [1][2][3][4][5][6][7]. Additionally, indoles are termed privileged motifs because of their excellent biological activities and applications in drug discovery.…”