Synthesis and Cytotoxic Evaluation of Carboxylic Acid-Functionalized Indenoisoquinolines

Abstract

In order to find out the influence of carboxylic acid functionalities in the N-lactam side chains of indenoisoquinolines on cytotoxic activities, several new compounds have been synthesized and structurally characterized by analytical and spectral methods. The incorporation of a carboxylic acid group into the lactam side chain of indenoisoquinolines results in differences in cytotoxicity. The results indicated that compound 18c displayed substantial cytotoxic specificity toward KB and HepG2 cancer cells.

Design and Synthesis of Indenoisoquinolines Targeting Topoisomerase I and Other Biological Macromolecules for Cancer Chemotherapy

“…A wide range of additional derivatives have been prepared and examined for cytotoxicity or for both cytotoxicity and Top1 inhibitory activities with results that are in general agreement with the expected outcomes based on documented structure–activity relationships . These have included both systems in which the scaffold is unsubstituted on the aromatic rings and the side chain is varied − as well as those that bear a variety of halogen, alkoxy, methylenedioxy, nitro, amino, and alkyl substituents on the aromatic rings. − However, indenoisoquinolines have also been prepared that are directed at targets other than Top1.…”

Synthesis, molecular docking analysis and in vitro evaluation of new heterocyclic hybrids of 4-aza-podophyllotoxin as potent cytotoxic agents

“…Heterocycles, a class of cyclic organic compounds containing at least one ring hetero atom, have played an important role in pharmaceutical development due to their variety of biological activities such as anti-fungal, 1 antimicrobial, 2 anti-inflammatory, 3,4 anti-diabetic, 5 cytotoxic, 6,7 anti-tumor, anti-cancer, 8,9 anti-viral, 10 acetylcholinesterase inhibitory, 11 and SARS-CoV2 inhibitory activities. 12 To date, heterocycles have presented themselves as the basic core of most marketed drugs.…”

Selective Blood Cell Hitchhiking in Whole Blood with Ionic Liquid-Coated PLGA Nanoparticles to Redirect Biodistribution After Intravenous Injection

“…This evidences a unique choline-PLGA surface “footprint” for each IL-PLGA coating assembly, while the negative surface charge indicates that the anion interfaces with the environment on the outermost layer of the coating (Table S1, Surface Charge). Additionally, we used a deuterated sodium trimethylsilylpropanesulfonate (DSS) standard to quantify the precise amount of total IL/mg PLGA and the molecular weights of the synthesized ILs, which allowed us to calculate a 24-hour IC50-biocompatible range 52 - 56 of approximate IL dosages (4.90 x 10 −7 to 3.50 x 10 −6 mol IL/100 μL dose for a ~25 mg mouse) for in-vivo administration (Table S3). Interestingly, anion hydrocarbon length played both a factor in the size of the coated nanoparticles (Table S2), as well as the amount of IL on the NP (Table S3), indicating that the bulkiness of the structure and likely sterics (from the location placement of double bond) played a role in the preferential assembly dynamics during nanoparticle coating.…”

“…This evidences a unique choline-PLGA surface "footprint" for each IL-PLGA coating assembly, while the negative surface charge indicates that the anion interfaces with the environment on the outermost layer of the coating (Table S1, Surface Charge). Additionally, we used a deuterated sodium trimethylsilylpropanesulfonate (DSS) standard to quantify the precise amount of total IL/mg PLGA and the molecular weights of the synthesized ILs, which allowed us to calculate a 24-hour IC50-biocompatible range [52][53][54][55][56] of approximate IL dosages (4.90 x 10 -7 to 3.50 x 10 -6 mol IL/100 µL dose for a ~25 mg mouse) for in-vivo administration (Table S3).…”