Fused pyrrolo-pyridines and pyrrolo-(iso)quinoline as anticancer agents

Mantu, Dorina; Antoci, Vasilichia; Sardaru, Monica C.; Matarneh, Cristina M. Al; Mangalagiu, Ionel I.; Danac, Ramona

doi:10.1515/psr-2021-0030

Cited by 4 publications

(4 citation statements)

References 123 publications

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“…Given the information discussed above, the focus of our current study is to synthesize new derivatives, building upon our previous research on N-heterocycle systems, [12][13][14] while remaining aligned with our keen interest in exploring chemical compounds with physiological activity. [15][16][17][18][19] This article presents our findings, including the synthesis, characterization, and antitumor evalution of several new N-heterocycle monoquaternary salts.…”

Section: Introductionmentioning

confidence: 99%

New monoquaternary salts of N-heterocycles: synthesis and antitumor assessment

SARDARU,

AL MATARNEH,

SIMIONESCU

et al. 2024

Rev.Roum.Chim.

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This manuscript presents the synthesis, structural characterization, and antitumor evaluation of new monoquaternary salts derived from various N-heterocycles. For quinoline and quinoxaline, respectively, unexpected H-bonded mixtures of the reactants have been obtained. To assess their potential antitumor activity, the comprehensive panel of NCI's 60 human cancer cell lines was employed. Remarkably, mixtures 3g and 3h displayed significant inhibitory activity against leukemia, melanoma, and colon cancer cell lines. Furthermore, mixtures 3g and 3h displayed good cytotoxicity on MCF7 breast cancer cells, but not on normal fibroblasts, at 2.5x10-5 M, showing promise for therapeutic applications.

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Section: Introductionmentioning

confidence: 99%

New monoquaternary salts of N-heterocycles: synthesis and antitumor assessment

SARDARU,

AL MATARNEH,

SIMIONESCU

et al. 2024

Rev.Roum.Chim.

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“…In addition, several other pyrrolo[1,2- a ]pyrazine alkaloids, such as dibromofakelin and longamide B, exhibit multiple biological activities, including cytotoxicity [ 5 ]. Moreover, our group has reported pyrrole-fused heterocyclic derivatives with an indolizine, pyrrolopyridazine, pyrrolo(iso)quinoline, and pyrrolophenathroline core, with part of them showing considerable anticancer properties [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring Pyrrolo-Fused Heterocycles as Promising Anticancer Agents: An Integrated Synthetic, Biological, and Computational Approach

et al. 2023

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Five new series of pyrrolo-fused heterocycles were designed through a scaffold hybridization strategy as analogs of the well-known microtubule inhibitor phenstatin. Compounds were synthesized using the 1,3-dipolar cycloaddition of cycloimmonium N-ylides to ethyl propiolate as a key step. Selected compounds were then evaluated for anticancer activity and ability to inhibit tubulin polymerization in vitro. Notably, pyrrolo[1,2-a]quinoline 10a was active on most tested cell lines, performing better than control phenstatin in several cases, most notably on renal cancer cell line A498 (GI50 27 nM), while inhibiting tubulin polymerization in vitro. In addition, this compound was predicted to have a promising ADMET profile. The molecular details of the interaction between compound 10a and tubulin were investigated through in silico docking experiments, followed by molecular dynamics simulations and configurational entropy calculations. Of note, we found that some of the initially predicted interactions from docking experiments were not stable during molecular dynamics simulations, but that configurational entropy loss was similar in all three cases. Our results suggest that for compound 10a, docking experiments alone are not sufficient for the adequate description of interaction details in terms of target binding, which makes subsequent scaffold optimization more difficult and ultimately hinders drug design. Taken together, these results could help shape novel potent antiproliferative compounds with pyrrolo-fused heterocyclic cores, especially from an in silico methodological perspective.

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“…[ 2 , 3 ]. As a result of this approach, important advances have been achieved in antimicrobial therapy, some of the present drugs from the market have a hybrid structure ( Figure 1 ) and some hybrid structures are in different clinical trials ( Figure 2 ) [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…A literature survey revealed that azines are privileged scaffolds in current medicinal chemistry and drug discovery, possessing a large variety of biological activities, such as: antibacterial, antifungal, antiplasmodial and antimalarial, anthelmintic, antitubercular, antiviral, anticancer, anti-inflammatory, antihypertensive, diuretic, antithrombic, anticoagulant, antidepressant, anxiolytic, anticonvulsant, analgesic, antiulcer, antidiabetic, antihistaminic, etc. [ 4 , 5 , 6 , 7 , 8 ]. As a matter of fact, the greatest majority of the existing drugs from the market contain in their structure a nitrogen heterocycle, some of them being a hybrid structure ( Figure 1 ), which justifies the demand of the pharmaceutical industry for such drugs with nitrogen heterocycle skeleton.…”

Section: Introductionmentioning

confidence: 99%

Hybrid Azine Derivatives: A Useful Approach for Antimicrobial Therapy

et al. 2022

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Nowadays, infectious diseases caused by microorganisms are a major threat to human health, mostly because of drug resistance, multi-drug resistance and extensive-drug-resistance phenomena to microbial pathogens. During the last few years, obtaining hybrid azaheterocyclic drugs represents a powerful and attractive approach in modern antimicrobial therapy with very promising results including overcoming microbial drug resistance. The emphasis of this review is to notify the scientific community about the latest recent advances from the last five years in the field of hybrid azine derivatives with antimicrobial activity. The review is divided according to the main series of six-member ring azaheterocycles with one nitrogen atom and their fused analogs. In each case, the main essential data concerning synthesis and antimicrobial activity are presented.

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Fused pyrrolo-pyridines and pyrrolo-(iso)quinoline as anticancer agents

Abstract: This work emphasizes the synthesis strategies and antiproliferative related properties of fused pyrrolo-pyridine (including indolizine and azaindoles) and pyrrolo-(iso)quinoline derivatives recently reported in literature.

Cited by 4 publications

References 123 publications

New monoquaternary salts of N-heterocycles: synthesis and antitumor assessment

New monoquaternary salts of N-heterocycles: synthesis and antitumor assessment

Exploring Pyrrolo-Fused Heterocycles as Promising Anticancer Agents: An Integrated Synthetic, Biological, and Computational Approach

Hybrid Azine Derivatives: A Useful Approach for Antimicrobial Therapy

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