Phenothiazine and amide-ornamented novel nitrogen heterocyclic hybrids: synthesis, biological and molecular docking studies

Abstract

The synthesis of phenothiazine and amide-ornamented nitrogen heterocycles (25–34) has been accomplished utilizing a multi-step synthetic protocol and the structures have been established based on physical and spectral techniques.

Cerium immobilized carbon nitride: A proficient and recyclable catalyst to construct carbon–carbon double bonds in water

“…Phenothiazine, a fused tricyclic aromatic entity with nitrogen and sulfur heteroatoms in the middle six-membered ring, is one of the important structural units existing in a diverse range of bio-pertinent chemical entities and sensitizers. In continuation of our endeavors on methodology development and the synthesis of heterocyclic molecules, [63,[65][66][67][68][69][70] we initially synthesized phenothiazinylmethylenemalononitrile 4a from its corresponding phenothiazine-based carbaldehyde precursor 2a, synthesized from commercially available 10Hphenothiazine through hexylation followed by condensation and formylation (Vilsmeier-Haack reaction) strategies, and malononitrile with the use of sodium ethoxide in ethanol in order for its cytotoxicity evaluation against pancreatic cancer cells (Figure 8). Further, this chemical entity would act as an efficient intermediate for the development of potent biological agents as well, as various functionalization can be possible around the phenothiazine nucleus and nitrile functionalities.…”

Expedition of sulfur‐containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: A decade update

“…Additionally, this compound demonstrated less toxicity against normal human cells. 250 Additionally, it also indicated G0/G1 phase cell cycle arrest and caused apoptotic activity by caspase 3 activation.…”

“…In recent times, Sivaramakarthikeyan et al 250 achieved the synthesis of phenothiazine-amide ornamented nitrogen heterocycles and found that these hybrids have potential cytotoxicity against SW1990 and AsPCl.…”

“…Amongst the derivatives, 203 (Figure 28) bearing ethyl substitution on the phenothiazine nitrogen and unsubstituted amide unit demonstrated the best cytotoxicity with IC 50 values 15.7 ± 2.29 µM and 22.8 ± 4.24 µM against ASPC1 and SW1990, respectively. Additionally, this compound demonstrated less toxicity against normal human cells 250 . Later, Luan et al, established the development of phenothiazine scaffold coupled with diverse amines via a three‐carbon spacer and substantiated them for in vitro cytotoxicity against PC‐3 cells.…”

“…In recent times, Sivaramakarthikeyan et al 250 achieved the synthesis of phenothiazine‐amide ornamented nitrogen heterocycles and found that these hybrids have potential cytotoxicity against SW1990 and AsPCl. Amongst the derivatives, 203 (Figure 28) bearing ethyl substitution on the phenothiazine nitrogen and unsubstituted amide unit demonstrated the best cytotoxicity with IC 50 values 15.7 ± 2.29 µM and 22.8 ± 4.24 µM against ASPC1 and SW1990, respectively.…”