In this study, a series of novel 1,3,4-oxadiazole-benzimidazole derivatives were designed and synthesized. Their cytotoxic activities against five cancer cell lines, including A549, MCF-7, C6, HepG2, and HeLa, were evaluated by the MTT assay. The compounds 5b,c showed satisfactory potencies with much higher anticancer activity in comparison to the reference drug doxorubicin against the studied cancer cell lines. In vitro, enzymatic inhibition assays of aromatase (ARO) enzymes were performed. Molecular docking, molecular dynamics simulations, and binding free energy analyses were used to better understand the structure-activity connections and mechanism of action of the aromatase inhibitors. Two types of satisfactory 3D-QSAR (CoMFA and CoMSIA) models were generated, to predict the inhibitory activities of the novel inhibitors. Molecular docking studies were also carried out to find their binding sites and types of their interactions with the aromatase enzyme. Additionally, molecular dynamics simulations were performed to explore the most likely binding modes of compounds 5b,c with CYP19A1. 

https://pubs.acs.org/doi/pdf/10.1021/acsomega.2c01497

Design, Synthesis, and Molecular Modeling Studies of a Novel Benzimidazole as an Aromatase Inhibitor

Extracellular Vesicles during TriTryps infection: Complexity and future challenges.

In the current scenario of medicinal chemistry, quinoline plays a pivotal role in the design of new heterocyclic compounds with several pharmacological properties, so the search for new synthetic methodologies and their application in drug discovery has been widely studied. So far, many procedures have been performed for the preparation of quinoline scaffolds, among which Friedländer quinoline synthesis plays an important role in obtaining these heterocycles. The Friedländer reaction involves condensation between 2‐aminobenzaldehydes and keto‐compounds. The quinoline nucleus, once obtained through the Friedländer synthesis, has been extensively modified so that these derivatives can exhibit a large number of biological activities such as anticancer, antimalarial, antimicrobial, antifungal, antituberculosis, and antileishmanial properties. In this work, the focus is on the applicability of the Friedländer reaction in the synthesis of various types of bioactive heterocyclic quinoline compounds, which to date has not been reported in the context of medicinal chemistry. The main part of this review selectively focuses on research from 2010 to date and will present highlights of the Friedländer quinoline synthesis procedures and findings to address biological and pharmacological activities.

Friedlӓnder's synthesis of quinolines as a pivotal step in the development of bioactive heterocyclic derivatives in the current era of medicinal chemistry

Design, synthesis and biological evaluation of novel isoniazid hybrids

Inhibition of Caco-2 and MCF-7 cancer cells using chalcones: synthesis, biological evaluation and computational study.

Synthesis, anti-tuberculosis activity and QSAR study of 2,4-diarylquinolines and analogous polycyclic derivatives

3-aryl-indolinones derivatives as antiplasmodial agents: synthesis, biological activity and computational analysis

Microwave‐assisted synthesis of 2‐styrylquinoline‐4‐carboxylic acid derivatives to improve the toxic effect against Leishmania (Leishmania) amazonensis

Tuberculosis was discovered more than a century ago, and it is still a disease that presents difficulties in its treatment due to the appearance of new resistant strains. To design new antituberculosis agents with a quinoline structure, our group developed three-dimensional structure-activity relationship (3D-QSAR) models, based on Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA). Statistically robust models (q2>0.6; r2ncv>0.8; r2pred>0.7) and with good external predictability were obtained. We found that positions 2, 3, and 4 of the quinoline nucleus are directly related to the modulation of the growth inhibitory activity of Mycobacterium tuberculosis H37Rv. To validate the models, we synthesized twelve quinolines through the Friëdlander reaction and three indolinones. The synthesized compounds were evaluated in the growth inhibition of resistant H37Rv tuberculosis strains (rpoBS450L, katGdel, and gyrAD94K) and in nontuberculous strains (M. avium and M. abscessus). We found that the compound (Z)-4-((2-oxoindolin-3-ylidene)amino)-N-(thiazol-2-yl)benzenesulfonamide was active in all resistant strains; the compound 2-(1H-indol-3-yl)-4-methylquinoline was active on M. avium; and the compound 10-methyl-11H-indeno[1,2-b]quinoline was active on M. abscessus. These models are useful for the discovery of new compounds with inhibitory properties of M. tuberculosis H37Rv, and with potential applications in resistant and nontuberculous strains. 

Ayelen Luczywo

Papers

Synthesis, anti-tuberculosis activity and QSAR study of 2,4-diarylquinolines and analogous polycyclic derivatives

3-aryl-indolinones derivatives as antiplasmodial agents: synthesis, biological activity and computational analysis

Microwave‐assisted synthesis of 2‐styrylquinoline‐4‐carboxylic acid derivatives to improve the toxic effect against Leishmania (Leishmania) amazonensis

QSAR‐Guided Study for the Microwave‐Assisted Synthesis of 4‐Methylquinoline Derivatives with Antimycobacterial Activity