New ferrocenyl-thiaza heterocycle-containing hybrids: synthesis, spactral characterization and biological activity

[J. M. Denić]

269 str.

Biografija i bibliografija str.: 265-269. Biografija sa bibliografijom: str. 265-269.

Organic chemistry; Organometallic chemistry; Medicinal chemistry

Herein, 36 new multitarget ferrocene (Fc) hybrids tethered with a small azathia heterocycle were synthesized and fully characterized. These compounds are grouped in 3 combinatorial libraries (CL). CL-1 consists of chloroquine (1) derivatives upgraded with an Fc moiety and privileged 1,3-thiazolidin-4-one/1,3-thiazinan-4-one scaffolds. Hybrids in CL-2 were obtained by substituting the propiolamide side chain in the lead compound ACL67 (6) with various acyl groups and by bioisosterically replacing the phenyl ring with an Fc unit. CL-3 includes 3-ferrocenyltetrahydro-3H-thiazolo[3,4-a]pyrazine-5,8-diones with different alkyl and alkyl aryl substituents on N-7. Two selected representatives (98-cis and 101) were also crystallographically characterized. The synthesized compounds were evaluated for their in vitro antimicrobial activity. For the compounds from CL-1 and those CL-3 members obtained in sufficient quantities, in vitro anti-inflammatory activity was assessed, while CL-1 derivatives were also tested for in vitro antiplasmodial activity. For CL-2 hybrids, the in vitro antiproliferative effect was evaluated against MRC-5, HepG2, and MDA-MB-231 cell lines. Notably, hybrid 83 demonstrated greater potency than the parent chloroquine (1) toward Dd2 Plasmodium falciparum strain, while several other hybrids (79, 80, 81, and 107) manifested substantially improved immunomodulatory and/or antimicrobial properties. Compounds 93-cis and 94 were cytotoxic toward MRC-5 and HepG2 cell lines in the low micromolar concentration range, similar to the cisplatin and ALC67 (6). The study provides valuable structure-activity relationship (SAR) data, offering insights that could guide future research in developing new multitarget drugs for the treatment of diseases such as malaria or cancer, complicated by drug resistance, bacterial co-infection, and immune-driven pathologies.

ferocenil-analozi, multitarget lekovi, hlorohin, 1,3-tijazolidin-4-on, 1,3-tijazinan-4-on, metil-1,3-tijazolidin-4-karboksilat, tetrahidro-3H-tijazolo[3,4-a]pirazin-5,8-dion, antiplazmodijalna aktivnost, antimikrobna aktivnost, antiinflamatorna aktivnost, citotoksičnost, odnos struktura-aktivnost

ferrocenyl analogs, multitarget drugs, chloroquine, 1,3-thiazolidin-4-one, 1,3-thiazinan-4-one, methyl 1,3-thiazolidine-4-carboxylate, tetrahydro-3H-thiazolo[3,4-a]pyrazine-5,8-dione, antiplasmodial activity, antimicrobial activity, anti-inflammatory activity, cytotoxicity, structure-activity relationship (SAR)

54.057:[547.5+547.7(043.3); 543.42:[547.5+547.7(043.3)

P 003, P 390; P 395; P 004

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