Synthesis, Antimicrobial Activity, Anti‐HIV Activity, and Molecular Docking of Novel 5‐, 6‐ and 7‐Membered Ring (1H‐Pyrrol‐2‐yl)aminolactams

Abstract

An efficient method has been developed for the synthesis of novel 5‐, 6‐ and 7‐membered ring (1H‐pyrrol‐2‐yl)aminolactams 5 a–f. This method featured Ugi‐4‐center‐3‐component reaction (U4 C3 C) followed by a post‐transformation reaction. All the newly synthesized (1H‐pyrrol‐2‐yl)aminolactams 5 a–f have been screened against six microbial species and the results revealed that these lactams exhibited moderate to good activity. These lactams were also tested in an in vitro for their antiviral activity against of HIV‐1 and HIV‐2 replication using MT‐4 cells. The testing results showed that compound 5 f is the only compound in the set lactams exhibiting a significant inhibition against HIV‐1 replication in cell line with EC50 value of 2.74±1.08 μM (CC50 of 18.93±4.0 μM), and SI 6. In addition, the compound 5 f was docked with essential proteins of HIV‐1 and HIV‐2 reverses transcriptase (RT), including HIV‐1 and HIV‐2 integrases strand proteins (PDB ID: 1EP4, 1FK9, 1HNV, 1VRU, 3DLE, 3DLG, and 3MEC). The docking results revealed that important hydrogen bond interactions and hydrophobic interactions were found between the compound 5 f and the essential amino acids residues of HIV‐1 and HIV‐2 (RT) proteins.

Pyrroles as Privileged Scaffolds in the Search for New Potential HIV Inhibitors

“…Recently, cyclic amides, known as lactams, coupled with pyrrole have proven to be a promising group in the search for an anti-HIV drug candidate, as demonstrated by compound 38 (Figure 16) [83]. Within a set of six compounds, 38 was the only compound active at a noncytotoxic concentration, showing an EC 50 of 2.74 ± 1.08 µM (CC 50 18.93 ± 4.0 µM) against HIV-1; however, 38 was inactive against replication in the HIV-2 cell line (Table 3).…”

“…Within a set of six compounds, 38 was the only compound active at a noncytotoxic concentration, showing an EC 50 of 2.74 ± 1.08 µM (CC 50 18.93 ± 4.0 µM) against HIV-1; however, 38 was inactive against replication in the HIV-2 cell line (Table 3). The docking analysis carried out with crystal structures of RT of HIV-1 and HIV-2 suggested that compound 38 was a potent HIV-1 NNRTI agent [83]. In an attempt to obtain active compounds in cells infected by HIV-1, Yonn et al [82] synthesized new scaffolds of pyrrolo-pyridine derivatives (Figure 16).…”

Synthesis and in Vitro Anti-tumor Activity of Novel Spliced Compounds of Zidovudine and 4-Anilinoquinazolines

“…1.3 分子对接 分子对接已被证明是研究蛋白质和小分子配体相 互作用的有效工具 [17] . 根据化合物 8a～8r 的细胞活性 和 EGFR 抑制活性结果, 化合物 8a、 8l 对 HepG2、 A549、 Hela、MCF-7、A549/DDP 细胞均具有良好的抑制活性, 且它们对 EGFR 在 0.01 μmol/L 浓度下的抑制作用较弱, 在高浓度下对 EGFR 又具有良好的抑制作用.…”