Synthesis, and reverse screening of 6‐(3,4,5‐trimethoxyphenyl)pyrimidine‐5‐carbonitrile derivatives as anticancer agents: Part‐II

Abstract

In continuation to our previous studies on cyanopyrimidine derivatives as anticancer agents, we further designed, synthesized, and evaluated new 3,4,5-trimethoxy phenyl ring pendant sulfur-containing cyanopyrimidine derivatives (4a-m) with a particular lipophilic behavior. In this work, we have varied the chain length from isopropyl to isopentyl and evaluated their anticancer activities. To study the antiproliferative spectrum, in vitro evaluation was piloted against a panel of 60 cancer cell lines at the National Cancer Institute, United States. Compound 4g (NSC: D-813664) displayed the most promising broad-spectrum anticancer activity with high growth inhibition of various cell lines representing action against multiple cancers diseases. It showed percentage growth inhibition of 84.01 and 76.94 against SR leukemia and HCT-116 colon cancer cell lines. Absorption, distribution, metabolism, excretion, and toxicity studies and reverse screening were also performed to identify the potential targets of designed molecules. It was concluded that 6-(3,4,5-trimethoxyphenyl) pyrimidine-5-carbonitrile derivatives exhibited its anticancer activity through different targets and hence could be further structurally modified and optimized to develop more potent multi-targeting anticancer agents.

Amino acid and Dicyclohexylurea Linked Pyrazole Analogues: Synthesis, In Silico and In Vitro Studies

“…The skin permeability values of amino acid and DCU linked pyrazole analogues had good results due to their values between −3 and 6. These values better absorbed by the skin [39] …”

“…These values better absorbed by the skin. [39] Moreover, the toxicity risk parameters of amino acid and DCU linked pyrazole analogues were determined using pre-ADMET software. The amino acid linked pyrazole 3 a, 4 b, and DCU linked pyrazole 5 a were identified as mutagen.…”