Design, synthesis, and biological evaluation of novel morpholinated isatin–quinoline hybrids as potent anti‐breast cancer agents

Abstract

Keeping in view the emerging need for potent and safer anti‐breast cancer agents as well as the pharmacological attributes of isatin, quinolone, and morpholine derivatives, novel hydrazine‐linked morpholinated isatin–quinoline hybrids were designed, synthesized, and evaluated as anti‐breast cancer agents. The synthesized hybrid compounds were preliminarily screened against two breast cancer cell lines (MCF‐7 and MDA‐MB‐231). Almost all synthetics showed potent inhibitory potential against hormone‐positive MCF‐7 cells while being inactive against hormone‐negative MDA‐MB‐231 cells. Potent compounds were further evaluated against the L929 (noncancerous skin fibroblast) cell line and found to be highly selective for MCF‐7 cells over L929 cells. Cell cycle analysis confirmed that the most potent compound AS‐4 (MCF‐7: GI50 = 4.36 µM) causes mitotic arrest at the G2/M phase. Due to higher selectivity toward estrogen receptor alpha (ERα)‐dependent MCF‐7 cells, various binding interactions of AS‐4 with ERα are also streamlined, suggesting the capability of AS‐4 to completely block ERα. Overall, the study suggests that AS‐4 can act as a potential lead for further development of potent and safer anti‐breast cancer agents.

The development of thymol–isatin hybrids as broad-spectrum antibacterial agents with potent anti-MRSA activity

“…3). The cytotoxic evaluation of AS8 against normal murine fibroblast cells (L929) suggested its IC 50 value of 125 μM, which makes it highly selective for MRSA with a selectivity index of 65.78, thus making it safer for normal cells 34 (Table 2).…”

“…Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 100 units per mL penicillin, and 100 μg mL −1 streptomycin mixture were used to maintain the cell lines (L929: acquired from American Type Culture Collection, ATCC, USA) at 37 °C in a humidified (containing 5% CO 2 ) atmosphere. 34 MTT assay. 96-Well plates seeded with cells (5 × 10 3 cells per well) were treated with the serial dilutions of test compounds and the positive control paclitaxel (100 μL) for 72 h under same conditions used for maintaining cells.…”

“…Absorption changes were noted down using a microplate reader at 490 nm. 34 The cell viability was calculated using the following equation. Static biofilm formation assay.…”

1,2,3‐Triazole Derivatives as an Emerging Scaffold for Antifungal Drug Development against Candida albicans: A Comprehensive Review

“…Keeping in view the pharmacological profile of isatin [70,71] and 1,2,3-triazole nucleus, Dehwal et al designed and synthesised 5-Fluoro-1H-indole-2,3-dione-triazoles and evaluated for antifungal activity against the Candida albicans. Among them, compound 42 was found to be most potent antifungal agent against Candida albicans with MIC value of 0.0075 μmol/mL as compared with standard fluconazole (MIC value of 0.0051 μmol/mL).…”

Artemisinin‐isatin hybrids tethered via ethylene linker and their anti‐lung cancer activity

“…The combination of two or more pharmacophores into a single hybrid molecule with or without any linker is a promising strategy in drug development since hybrid molecules usually possess synergistic effects of all pharmacophores. [ 17,18 ] Hybridization of ART moiety with isatin pharmacophore appears to be a judicious strategy to develop novel effective candidates to combat cancers since ART‐isatin hybrids have the potential to act on multiple targets in lung cancer cells simultaneously, alongside their intrinsic versatility and unique physicochemical properties. [ 19,20 ] Several ART‐isatin hybrids have been developed in recent years, and the structure–activity relationships (SARs) proved that the linker between ART and isatin motifs was the main factor affecting the antiproliferative activity.…”