No abstract

This review article proposes a comprehensive report of the design strategies engaged in the development of various sulfur-bearing cytotoxic agents. The outcomes of various studies depict that the sulfur heterocyclic framework is a fundamental structure in diverse synthetic analogs representing a myriad scope of therapeutic activities. A number of five-, six-and seven-membered sulfur-containing heterocyclic scaffolds, such as thiazoles, thiadiazoles, thiazolidinediones, thiophenes, thiopyrans, benzothiazoles, benzothiophenes, thienopyrimidines, simple and modified phenothiazines, and thiazepines have been discussed. The subsequent studies of the derivatives unveiled their cytotoxic effects through multiple mechanisms (viz. inhibition of tyrosine kinases, topoisomerase I and II, tubulin, COX, DNA synthesis, and PI3K/Akt and Raf/MEK/ERK signaling pathways), and several others. Thus, our concise illustration explains the design strategy and anticancer potential of these five-and six-membered sulfur-containing heterocyclic molecules along with a brief outline on seven-membered sulfur heterocycles. The thorough assessment of antiproliferative activities with the reference drug allows a proficient assessment of the structure-activity relationships (SARs) of the diversely synthesized molecules of the series.

Objective: To synthesize a series of phenanthrene-thiazolidinedione hybrids and explore their cytotoxic potential against human cancer cell lines of A-549 (lung cancer), HCT-116 and HT-29 (colon cancer), MDA MB-231 (triple negative breast cancer), BT-474 (breast cancer) and (mouse melanoma) B16F10 cells. Methods: A new series of phenanthrene-thiazolidinedione hybrids was synthesized via Knoevenagel condensation of phenanthrene-9-carbaldehyde and N-alkylated thiazolidinediones. The cytotoxicity (IC50) of the synthesized compounds was determined by MTT assay. Apoptotic assays like (AO/EB) and DAPI staining, cell cycle analysis, JC-1 staining and Annexin V binding assay studies were performed for the most active compound (Z)-3-(4-bromobenzyl)-5-((2,3,6,7- tetramethoxyphenanthren-9-yl)methylene)thiazolidine-2,4-dione (17b). Molecular docking, dynamics and evaluation of pharmacokinetic (ADME/T) properties were also carried out by using Schrödinger. Results and Discussion: From the series of tested compounds, 17b unveiled promising cytotoxic action with IC50 value of 0.985 ± 0.02 μM on HCT-116 human colon cancer cells. The treatment of HCT-116 cells with 17b demonstrated distinctive apoptotic morphology like shrinkage of cells, horseshoe shaped nuclei formation and chromatin condensation. Flow-cytometry analysis revealed the G0/G1 phase cell cycle arrest in a dose dependent fashion. The AO/EB, DAPI, DCFDA, Annexin-V and JC-1 staining studies were performed in order to determine the effect of compound on cell viability. Computational studies were performed by using Schrödinger to determine the stability of the ligand with the DNA. Conclusion: The current study provides an insight on developing a series of phenanthrene thiazolidinedione derivatives as potential DNA interactive agents which might aid in colon cancer therapy.

The unprecedented efficiency, reliability and adaptability in drug discovery, with the growing number of applications and impact, have made Click Chemistry fascinating to the scientific community. The specificity, biocompatibility along with other principles of click chemistry offers a reliable platform for the synthesis of drug-like molecules that can expedite the drug discovery process. This account summarizes such successes of versatile click reactions from our research group towards the development of functional molecules.

No abstract

A facile and proficient dithiocarbamation of imidazo[1,2-a]pyridines and other imidazoheterocycles with in situ generated dithiocarbamates is established using a water-soluble, stable copper(I) catalyst and molecular oxygen under microwave conditions. The...

A facile microwave‐assisted synthetic strategy for the construction of C–C bond via regioselective Friedel–Crafts arylation of 3‐hydroxy‐3‐phenylethynyl oxindoles with different electron‐rich nucleophiles such as phenols, sulphonamides, anisole, benzofuran, and benzothiophene has been established by employing BF3 ⋅ OEt2 as catalyst. The current protocol attributes mild conditions, cost‐effective, transition‐metal free synthesis, wide substrate scope and moderate to good yields. Moreover, this method is amenable for the generation of a library of densely substituted 3‐(4‐hydroxyphenyl)‐3‐(phenylethynyl) oxindoles and 3‐(4‐benzenesulphonamide)‐3‐(phenylethynyl) oxindoles as privileged scaffolds.

No abstract