Cancer remains a leading cause of death worldwide, resulting in continuous efforts to discover and develop highly efficacious anticancer drugs. High‐throughput screening of heterocyclic compound libraries is one of the promising approaches that provided several new lead molecules with a novel mechanism of action. On the basis of the promising anticancer potential of imidazoquinoxaline as well as the structurally similar imidazoquinoline‐derived scaffold, we prepared a set of C6‐substituted benzimidazo[1,2‐a]quinoxaline derivatives via two novel synthetic routes using commercially available starting materials, with good to excellent yields and evaluated their anticancer activity against the NCI‐60 cancer cell lines. The one‐dose (10 µM) anticancer screening of the synthesized compounds in the NCI‐60 cell line panel revealed that the substituents have a significant role in the activity. In particular, the indole (7f), imidazole (7g), and benzimidazole (7h) derivatives showed significant activity against the triple‐negative breast cancer cell line, MDA‐MB‐468. The lead compounds also exhibited notable IC50 values against another breast cancer cell line, MCF‐7. Furthermore, it was observed that these compounds were relatively nontoxic to normal cell lines: HEK293 (human embryonic kidney cell line) and MCF12A (nontumorigenic human breast epithelial cell line). The IC50 values against healthy cells were at least 5‐ to 11‐fold higher, offering a new class of heterocycles that can be further developed as promising therapeutics for cancer treatment.

In this article, we report the chemical synthesis of pyochelin-zingerone conjugate via a hydrolysable ester linkage for drug delivery as a "Trojan Horse Strategy." It is a new therapeutic approach to combat microbial infection and to address the issue of multi drug resistance in Gram-negative, nosocomial pathogen Pseudomonas aeruginosa.Pyochelin (Pch) is a catecholate type of phenolate siderophore produced and utilized by the pathogen P. aeruginosa to assimilate iron when colonizing the vertebrate host.Zingerone, is active component present in ginger, a dietary herb known for its antivirulent approach against P. aeruginosa. In the present study, zingerone was exploited to act as a good substitute for existing antibiotics, known to have developed resistance by most pathogens. Encouraging results were obtained by docking analysis of pyochelin-zingerone conjugate with FptA, the outer membrane receptor of pyochelin. Conjugate also showed anti-quorum sensing activity and also inhibited swimming, swarming, and twitching motilities as well as biofilm formation in vitro.

In the present work, 4‐hydroxy enigmol (1), an analogue of enigmol which is a known orally bioavailable 1‐deoxysphingolipid, effective against multiple cancer cell lines, has been synthesized with an additional hydroxy group for improved anti‐cancer activity. The additional group in compound (1) is likely to show enhanced activity due to improved cell permeability and hydrophilicity. The key steps involved are stereoselective cross metathesis reaction and OsO4/NMO mediated dihydroxylation. Further, analogues of 4‐hydroxy enigmol (1) with varying chain lengths (2, 3) have also been synthesized using the same synthetic strategy for varying hydrophobicity as an additional structural feature. To support the genesis in the design of compound (1–3), the pharmacokinetic studies and docking analysis has been done for calculating the polar surface area, binding affinity and hydrophobicity/hydrophilicity. The preliminary in‐vitro cytotoxicity on cancer cell lines displayed promising activity against the PC‐3 cell lines and HCT‐116 cell lines.

1-Deoxysphingolipids are a class of sphingolipids which lacks the primary hydroxyl group (C1-OH). Hence, it does not get converted/degraded to complex corresponding products like sphingosine-1-phosphate (SIP), a pro-mitotic. Enigmol, an orally bioavailable 1-deoxyphingolipid has shown potential against various different types of cancer cells along with impressive cytotoxic/antiproliferative properties. Due to its unique structural properties, Enigmol and its analogs have attracted considerable attention from synthetic organic chemists. This review provides an overview of all the synthetic approaches being followed for the synthesis of Enigmol and its structural analogs.

In the present work, a small library of few 1‐deoxysphingolipid ceramides has been designed and synthesized via an efficient UGI multicomponent reaction. The deoxy sphingosine intermediate (10) synthesized via Grignard reaction and olefin metathesis reaction was used as the amine component with cyclohexyl isocyanide and various aldehydes. The butyric acid has been used as an acid component which may turn out be an advantage due to the chemo preventive properties of the acid formed after the partial hydrolysis of the ceramide. Compounds (1‐6) has been synthesised via a short and facile route in high purity and yield. Molecular docking of all the analogues has been carried out with protein Sphingosine Kinase I using BiopredictaVlife MDS tool to determine the relative docking score and ligand‐protein interactions. Further in vitro studies were performed on PC‐3 (prostate cancer) and HCT‐116 (colon cancer) cell lines in which four compounds (1‐4) showed reasonable anti‐cancer activity against both the cell lines while compound (3) showed highest activity with IC50 value of 0.344 μM against PC‐3 (prostate cancer) cell lines and 0.624 μM against HCT‐116 (colon cancer) cell lines. Compound (4) showed IC50 value of 0.472 μM against HCT‐116 (colon cancer) cell lines.