Positions C3 Research Articles

Chemical characterization of ceramides isolated from a gliding marine bacterium Aureispira marina.

Ceramides containing 2-hydroxy fatty acids were purified from a gliding marine bacterium Aureispira marina, and their chemical structure was investigated. The ceramide molecules contained 2-hydroxy-15-methyl-hexadecanoic acid and 2-hydroxy-15-methyl-hexadecenoic acid, and the double bond of the latter fatty acid was proved to be located between the positions C3 and C4. The major portion of these 2-hydroxy fatty acids was determined to have D-configuration (S-configuration) after diastereomeric derivatization. Three carbon skeletons were found in sphingosines from ceramides, ie (1) 1,3-dihydroxy-2-amino-4-octadecen, (2) 1,3-dihydroxy-2-amino-17-methyl-4-octadecen, and (3) 1,3-dihydroxy-2-amino-9-methyl-4-octadecen. Molecules with additional double bonds were found in sphingosines with structures 1 and 3. The presence of ceramides with these chemical characteristics would be a significant feature for the taxonomy of A. marina and related bacteria.

Four new tin(II), uranyl(II), vanadyl(II), and zirconyl(II) alloxan biomolecule complexes: synthesis, spectroscopic and thermal characterizations

ABSTRACT. The alloxan as a biomolecule ligand has been utilized to synthesize thermodynamically and kinetically stabilized four new tin(II), uranyl(II), vanadyl(II), and zirconyl(II) complexes. In the complexes, tin(II) ion present is in tetrahedral arrangement, zirconyl and vanadyl(II) ions present are in square pyramid feature but uranyl(II) ion present is in octahedral arrangement and all are coordinated by two bidentate alloxan ligand in complexes. The synthesized alloxan ligand coordinate with central metal(II) ion through oxygen in position C2=O and the nitrogen in position N1 developing a 4-membered chelate ring. Synthesized Sn(II), UO2(II), VO(II), and ZrO(II) complexes via bidentate ligand have been accurately described by various spectroscopic techniques like elemental analysis (C, H, N, metal), conductivity measurements, FT-IR, UV-Vis, 1H-NMR, and TGA. The kinetic thermodynamic parameters such as: E*, ΔH*, ΔS* and ΔG* were calculated using Coats and Redfern and Horowitz and Metzger equations.
 
 KEY WORDS: Alloxan, Metal ions, Spectroscopy, Ligand, Coordination, Thermogravimetry
 
 Bull. Chem. Soc. Ethiop. 2022, 36(2), 373-385. 
 DOI: https://dx.doi.org/10.4314/bcse.v36i2.11

Long‐Term Energy Storage Systems Based on the Dihydroazulene/Vinylheptafulvene Photo‐/Thermoswitch

AbstractThe dihydroazulene/vinylheptafulvene (DHA/VHF) couple presents a photo‐/thermoswitch that has attracted interest for the development of molecular solar thermal energy storage systems. Here we present the synthesis and optical properties as well as the switching properties of DHA derivatives incorporating alkyne and norbornadiene (NBD) substituents at position C2. The corresponding VHF isomers exhibited remarkably long lifetimes. Thus, the VHF‐to‐DHA back‐reaction half‐life for a derivative with a phenylethynyl substituent was 22 days in acetonitrile at room temperature, while the half‐life of a VHF reference compound having a phenyl substituent is around 3.5 h under the same conditions. This finding is particularly attractive in the quest for long‐term energy storage systems, considering limited enhancement of molecular weight and maintenance of good quantum yield photoisomerization. Moreover, from the thermal back‐reaction of an NBD compound, used as a precursor for the DHA‐NBD dyad, we estimated the radical‐stabilizing influence of a C(Me)=C(CN)2 substituent.

Total Synthesis of the Alleged Structure of (+)-Fimbricalyxoid A

An enantioselective total synthesis of the alleged structure of (+)-fimbricalyxoid A is reported. The synthetic strategy features a pyridine-N-oxidate-mediated SN2' reaction to introduce an oxygen functionality at position C3 of the A-ring and a sequential three-step process via the cleavage of the C-O bonds and hemiketalization to form the 3,20-oxybridge. With this strategy, the target molecule was synthesized in 19% overall yield and 12 steps from our previously synthesized cis-fused octahydrophenanthrene (+)-6.

Metabolic Activation and Cytotoxicity of Propafenone Mediated by CYP2D6.

Propafenone (PPF) is a class IC antidysrhythmic drug, which is commonly used for the treatment of atrial fibrillation and other supraventricular arrhythmias. It is also a β-adrenoceptor antagonist that can cause bradycardia and bronchospasm. Hepatotoxicity is one of the adverse reactions reported, with clinical manifestations including acute cholestasis and hepatocyte necrosis. However, the mechanism of PPF-induced hepatotoxicity remains unclear. The present study was conducted to identify reactive metabolite(s) to determine related metabolic pathways and define the possible association of the bioactivation with PPF cytotoxicity. An O-demethylation phase I metabolite (M1), a further position C5 hydroxylation (para-position of the benzene ring) metabolite (M2), glutathione (GSH) conjugates (M3 and M4), and N-acetylcysteine (NAC) conjugates (M5 and M6) were detected in rat liver microsomal incubations containing PPF and GSH or NAC as trapping agents. The corresponding GSH conjugates and NAC conjugates were found in the bile and urine of rats after PPF administration, respectively. The observed GSH and NAC conjugates indicate that a quinone metabolite was generated in vitro and in vivo. Recombinant P450 enzyme incubations showed that CYP2D6 was the principal enzyme catalyzing this metabolic activation. Quinidine, a selective inhibitor of CYP2D6, attenuated the susceptibility of hepatocytes to the cytotoxicity of PPF. The results suggest that PPF was metabolized to a p-quinone intermediate which may be involved in PPF-induced hepatotoxicity.

Exploring the Biosynthetic Potential of TsrM, a B12 -dependent Radical SAM Methyltransferase Catalyzing Non-radical Reactions.

B12 -dependent radical SAM enzymes are an emerging enzyme family with approximately 200,000 proteins. These enzymes have been shown to catalyze chemically challenging reactions such as methyl transfer to sp2- and sp3-hybridized carbon atoms. However, to date we have little information regarding their complex mechanisms and their biosynthetic potential. Here we show, using X-ray absorption spectroscopy, mutagenesis and synthetic probes that the vitamin B12 -dependent radical SAM enzyme TsrM catalyzes not only C- but also N-methyl transfer reactions further expanding its synthetic versatility. We also demonstrate that TsrM has the unique ability to directly transfer a methyl group to the benzyl core of tryptophan, including the least reactive position C4. Collectively, our study supports that TsrM catalyzes non-radical reactions and establishes the usefulness of radical SAM enzymes for novel biosynthetic schemes including serial alkylation reactions at particularly inert C-H bonds.

1H-Pyrazolo[3,4-b]pyridines: Synthesis and Biomedical Applications.

Pyrazolo[3,4-b]pyridines are a group of heterocyclic compounds presenting two possible tautomeric forms: the 1H- and 2H-isomers. More than 300,000 1H-pyrazolo[3,4-b]pyridines have been described which are included in more than 5500 references (2400 patents) up to date. This review will cover the analysis of the diversity of the substituents present at positions N1, C3, C4, C5, and C6, the synthetic methods used for their synthesis, starting from both a preformed pyrazole or pyridine, and the biomedical applications of such compounds.

Synthesis of Quinolino[1,2-c]quinazolin-6-one Derivatives via Formal (4+2)-Cycloaddition of Alkenes to Quinazolinе-Derived N-Acyliminium Cations: An Experimental and Theoretical Study

Abstract3-Aryl-4-hydroxy-1-methyl-3,4-dihydroquinazolin-2(1H)-ones were synthesized by reduction of 3-aryl-1-methylquinazoline-2,4(1H,3H)-diones with sodium triethylborohydride and studied as precursors of N-acyliminium cations that were expected to be trapped with various alkenes as (4+2)-cycloadducts. Unsubstituted 3-aryl-4-hydroxy-1-methyl-3,4-dihydroquinazolin-2(1H)-ones in the presence of BF3·Et2O failed to produce the desired cycloadducts probably due to a homooligomerization reaction involving N-acyliminium intermediates. To prevent this side reaction, we found it necessary to introduce substituents at both positions C6 and C8 of the quinazoline ring and C4′ of the 3-phenyl substituent. Utilizing bromine atoms as substituents at C6 and C8, N-acyliminium cations generated from 3-aryl-6,8-dibromo-4-hydroxy-1-methyl-3,4-dihydroquinazolin-2(1H)-ones in the presence of BF3·Et2O smoothly reacted with such alkenes as indene, acenaphthylene, styrene, α-methylstyrene to give new quinolino[1,2-c]quinazolin-6-one derivatives with high regio- and stereoselectivity. Density functional theory calculations were performed at the M06-2x/cc-pVDZ level to obtain an insight into the mechanism of the (4+2)-cycloaddition reaction of quinazoline-derived N-acyliminium cations to alkenes.

Glycoconjugate content quantification to assess vaccine potency: A simplified approach

Several glycoconjugate vaccines have been licensed or are currently in clinical development to prevent bacterial infections.Here we report the development of a single analytical assay to quantify the conjugated saccharide content, as alternative to two separated total and free (unconjugated) saccharide assays used so far, for a quadrivalent conjugate vaccine containing meningococcal serogroup A polysaccharide (α-1,6-linked N-acetylmannosamine phosphate repeating unit partly O-acetylated at position C3 or C4) coupled with CRM197 protein.The results confirm a high linear correlation among the two approaches (conjugated saccharide content vs. difference of total saccharide and free saccharide).Conjugated saccharide content estimation is therefore demonstrated to be a suitable method to monitor the product quality of vaccines containing meningococcal serogroup A conjugate antigen, in the final filled presentation as demonstrated here and potentially on the bulk conjugate before formulation.

Betulin Attenuates TGF-β1- and PGE<sub>2</sub>-Mediated Inhibition of NK Cell Activity to Suppress Tumor Progression and Metastasis in Mice

Transforming growth factor (TGF)-β1 and prostaglandin E2 (PGE2) are humoral factors critically involved in the induction of immunosuppression in the microenvironment of various types of tumors, including melanoma. In this study, we identified a natural compound that attenuated TGF-β1- and PGE2-induced immunosuppression and examined its effect on B16 melanoma growth in mice. By screening 502 natural compounds for attenuating activity against TGF-β1- or PGE2-induced suppression of cytolysis in poly(I:C)-stimulated murine splenocytes, we found that betulin was the most potent compound. Betulin also reduced TGF-β1- and PGE2-induced downregulation of perforin and granzyme B mRNA expression and cell surface expression of NKG2D and CD69 in natural killer (NK) cells. Cell depletion and coculture experiments showed that NK cells, dendritic cells, B cells, and T cells were necessary for the attenuating effects of betulin. Structure-activity relationship analysis revealed that two hydroxyl groups at positions C3 and C28 of betulin, their cis-configuration, and methyl group at C30 played crucial roles in its attenuating activity. In a subcutaneous implantation model of B16 melanoma in mice, intratumor administration of betulin and LY2157299, a TGF-β1 type I receptor kinase inhibitor, significantly retarded the growth of B16 melanoma. Notably, betulin increased significantly the number of CD69 positive NK cells in tumor sites at early stages of post-tumor cell injection. Our data suggest that betulin inhibits the growth of B16 melanoma by enhancing NK cell activity through attenuating the immunosuppressive tumor microenvironment.

Determination of the structure and in vitro anticancer activity of fucan from Saccharina dentigera and its derivatives

The fucoidan SdeF was isolated from brown alga Saccharina dentigera. The structure of the obtained polysaccharide was studied by chemical methods, NMR spectroscopy of the fully and partially desulfated derivatives, and mass spectrometry of the fucoidan fragments, labeled with 18O. The SdeF was shown to be sulfated (40%) 1,3-linked α-L-fucan, with branches at C2. The sulfate groups were found at positions C2 and C4. Derivatives SdeFDS and SdeFPL were obtained by solvolytic desulfation and autohydrolysis of SdeF, respectively. According to 13C NMR data, SdeFDS is 1,3-linked α-L-fucan, while SdeFPL is 4-sulfated 1,3-linked α-L-fucan. Native fucoidan SdeF was shown to be a non-toxic anticancer substance in the model of human malignant melanoma RPMI-7951, colorectal adenocarcinoma HCT-116, and small intestine adenocarcinoma HuTu 80 cells. The partial desulfation of SdeF at C2 and/or the reduction of its Mw, from 229 to 28 kDa, decreased the anticancer activity; complete removal of the sulfated groups and/or Mw reduction to 4.7 kDa further reduced the effect of this polysaccharide.

Clinical application of liver diseases diagnosis using ultrahigh-sensitive liquid chromatography-mass spectrometry for sialic acids detection

Sialic acids are a group of nine-carbon N-acetylated derivatives of neuraminic acid containing a keto group at position C2 (ketononose), which play important roles in many biological processes. The simultaneous detection of free sialic acid (FSA) and total sialic acid (TSA) is always challenging due to three orders of magnitude difference. An accurate and robust chemical derivatization-based liquid chromatography-mass spectrometry (LC-MS) method was proposed here to quantify both TSA and FSA in human serum with only 1 μL human serum consumption. The derivatization method with Girard's P (GP) reagent provided an ultrasensitive analysis of sialic acids as only [GP+SA-H2O]+ ions derivatized from SA could be detected by LC-MS. The limit of quantification (LOQ) of SA was less than 5 fg (S/N = 47), which was the most sensitive measurement published for SAs in biomatrices. In addition, no matrix effect existed after 10000-fold dilution of serum extracts. The recovery rates were in the range of 98.1–114.0% and the coefficient of variations (CV) was within 5%. The method has been successfully applied for the quantification of TSA and FSA in serums of patients with different liver diseases. The specificities of TSA and FSA for the early diagnosis of severe hepatopathies were higher than most of the lab blood test indicators with area under the curve (AUC) of 0.900 and 0.882.

Identification and release kinetics of peptides from tilapia skin collagen during alcalase hydrolysis

Collagen from tilapia skin was extracted and confirmed as type I collagen. Collagen was then hydrolyzed with alcalase for 4 h and the released peptides were identified. The structure–activity relationship of collagen-released peptides showed that proline at position C3 played a key role in improving ACE inhibitory activity, while proline at position C2 had a negative effect. Collagen peptide release kinetics showed that with the extension of time, the number of peptides increased dramatically at first, decreased, and then tended to be stable. This indicated that collagen peptides mainly originated from primary enzymolysis at the first stage and began to undergo secondary hydrolysis in the second stage. Afterwards, secondary enzymolysis was dominant at the third stage and finally remained stable at final two stages. Understanding the pattern of collagen peptide release kinetics might offer a powerful approach in the collagen-peptide food processing industry to better control food safety and quality.

Determination of the semiexperimental equilibrium structure of 2-acetylthiophene in the presence of methyl internal rotation and substituent effects compared to thiophene.

The microwave spectra of thiophene and 2-acetylthiophene were recorded in the frequency range from 2 to 40 GHz using two molecular jet Fourier transform microwave spectrometers. For 2-acetylthiophene, two conformers with a syn and an anti orientation of the S1-C2 and C6O bonds (with respect to the C2-C6 bond) were identified, and the syn-conformer was more stable. The spectra of the 34S- and 13C-isotopologues of syn-2-acetylthiophene were also assigned, and the semiexperimental equilibrium structure could be determined. Compared to thiophene, at the substitution position, the S1-C2 and C2C3 bond lengths both increase by about 0.007 Å, and the bond angle S1-C2C3 decreases by 0.06°, noticeably larger than the experimental uncertainties. A-E torsional splittings were observed due to internal rotation of the methyl group hindered by a barrier height of 330.187(35) and 295.957(17) cm-1 for the syn-conformer and the anti-conformer, respectively. Geometry and internal rotation parameters are compared with those of related thiophene derivatives, as well as those of furan and 2-acetylthiophene to gain a better understanding of structure determination in the presence of methyl internal rotation.

Genoprotective Effect of Some Flavonoids against Genotoxic Damage Induced by X-rays In Vivo: Relationship between Structure and Activity.

Flavonoids constitute a group of polyphenolic compounds characterized by a common gamma-benzo- pyrone structure considered in numerous biological systems to possess antioxidant capacity. Among the different applications of flavonoids, its genoprotective capacity against damage induced by ionizing radiation stands out, which has been related to antioxidant activity and its chemical structure. In this study, we determined the frequency of appearance of micronucleus in vivo by means of the micronucleus assay. This was conducted in mice treated with different flavonoids before and after exposure to 470 mGy X-rays; thereafter, their bone marrow polychromatophilic erythrocytes were evaluated to establish the structural factors enhancing the observed genoprotective effect. Our results in vivo show that the presence of a monomeric flavan-3-ol type structure, with absence of carbonyl group in position C4 of ring C, absence of conjugation between the carbons bearing the C2 = C3 double bond and the said ring, presence of a catechol group in ring B and characteristic hydroxylation in positions 5 and 7 of ring A are the structural characteristics that determine the highest degree of genoprotection. Additionally, a certain degree of polymerization of this flavonoid monomer, but maintaining significant levels of monomers and dimers, contributes to increasing the degree of genoprotection in the animals studied at both times of their administration (before and after exposure to X-rays).

Photoreactivity and stability of flavonoid yellows used in cultural heritage

Flavonoid yellows are historical dyes widely found in cultural heritage, in particular those based on the glycosides of luteolin, quercetin and kaempferol. In this research, for the first time, the photodegradation quantum yields (ΦR) were calculated for luteolin, quercetin and kaempferol as well as their glycosides Lut-7-O-Glc, Que-3-O-Glr, Kaem-3-O-Glc and compared to the reactivity of eriodictyol. The results are discussed within the current state of the art on the mechanisms of degradation for these antioxidant compounds, which are reviewed in the introduction. ΦR values were obtained in solution irradiating at 313 nm and 366 nm, providing the quantification of the stability of flavonoid yellows. In particular, by irradiating at 366 nm, a very good stability scale is obtained, with ΦR values for luteolin and the 3-O-glycosides of quercetin and kaempferol on the order of 10−6. The more reactive quercetin and kaempferol are characterized by ΦR values of ca. 3 × 10−5. The relative stability of these yellows can be explained by a photoprotective mechanism based on excited state proton transfer, which is more efficient when there is an OH in the C5 position. In addition, electron transfer, and consequently oxidation, is also enhanced through the OH in position C3 when compared to C5.Solvents effects were also studied and to mimic the environment of the dye in wool, irradiation at 366 nm in a proteinaceous gel was carried out. In this gel, the ΦR values increased for all the molecules studied, reaching 1 × 10−4 and 2 × 10−4 for kaempferol and quercetin, respectively. This drastic enhancement shows that the environment has a major impact on stability. The main degradation products were also studied by irradiation with a xenon source (λirr ≥ 300 nm), and characterized by HPLC-DAD-MS and LC-HRMS/MS. These data, on the reaction mechanism, show that the double bond between C2 and C3, in the C ring, is the most reactive point of the molecules, as in all the flavonoids degradation started by solvent attack, followed in some cases by ring opening and the formation of low molecular weight hydroxyl compounds such as benzoic acids, in agreement with the general reaction scheme proposed in literature.

CHNQD-00603 Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by the miR-452-3p-Mediated Autophagy Pathway.

Background: Periodontitis is a chronic and progressive disease accompanied by bone loss. It is still a challenge to restore the bone structure. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a decisive role in bone restoration and regeneration. Marine natural products (MNPs) have multiple biological activities, including anti-tumor and anti-inflammatory properties. However, the exploration of MNPs in osteogenesis is far from sufficient. Methods: We obtained a series of derivatives through structural optimization from 4-phenyl-3,4-dihydroquinolin-2(1H)-one alkaloid isolated from Scopulariopsis sp. Some preliminary cytological experiments showed that CHNQD-00603, obtained by adding a methoxy group to the position C3 and a hydroxyl group to the position C4 of 4-phenyl-3,4-dihydroquinolin-2(1H)-one, might promote the osteogenic differentiation of BMSCs. To further investigate the effects of CHNQD-00603 on BMSCs, we performed a CCK-8 assay and qRT-PCR, alkaline phosphatase staining (ALP), and alizarin red S staining to assess the cytotoxicity and the ability of osteogenic differentiation of CHNQD-00603. The autophagy level was assessed and validated by WB, qRT-PCR, and transmission electron microscopy. Then, 3-methyladenine (3-MA) was added to further examine the role of autophagy. Based on the expression of autophagy-related genes, we predicted and examined the potential miRNAs by bioinformatics. Results: CCK-8 assay showed that CHNQD-00603 at 1 µg/ml did not influence BMSCs activity. However, the proliferation rate decreased from the seventh day. qRT-PCR, ALP staining, ALP activity assay, and Alizarin red S staining showed that the best concentration of CHNQD-00603 to promote osteogenic differentiation was 1 µg/ml. Further investigations indicated that CHNQD-00603 activated autophagy, and the inhibition of autophagy by 3-MA attenuated CHNQD-00603-enhanced osteogenic differentiation. Subsequently, the findings from bioinformatics and qRT-PCR indicated that miR-452-3p might be a regulator of autophagy and osteogenesis. Furthermore, we transfected BMSCs with miR-452-3p NC and mimics separately to further determine the function of miR-452-3p. The data showed that the overexpression of miR-452-3p moderated the level of autophagy and osteogenic differentiation of CHNQD-00603-treated BMSCs. Conclusion: Our data suggested that CHNQD-00603 promoted the osteogenic differentiation of BMSCs by enhancing autophagy. Meanwhile, miR-452-3p played a regulatory role in this process.

Design, Synthesis, Biological Evaluation and Silico Prediction of Novel Sinomenine Derivatives

Sinomenine is a morphinan alkaloid with a variety of biological activities. Its derivatives have shown significant cytotoxic activity against different cancer cell lines in many studies. In this study, two series of sinomenine derivatives were designed and synthesized by modifying the active positions C1 and C4 on the A ring of sinomenine. Twenty-three compounds were synthesized and characterized by spectroscopy (IR, 1H-NMR, 13C-NMR, and HRMS). They were further evaluated for their cytotoxic activity against five cancer cell lines, MCF-7, Hela, HepG2, SW480 and A549, and a normal cell line, Hek293, using MTT and CCK8 methods. The chlorine-containing compounds exhibited significant cytotoxic activity compared to the nucleus structure of sinomenine. Furthermore, we searched for cancer-related core targets and verified their interaction with derivatives through molecular docking. The chlorine-containing compounds 5g, 5i, 5j, 6a, 6d, 6e, and 6g exhibited the best against four core targets AKT1, EGFR, HARS and KARS. The molecular docking results were consistent with the cytotoxic results. Overall, results indicate that chlorine-containing derivatives might be a promising lead for the development of new anticancer agents.

The theoretical investigation of monohydroxy flavone: A combined DFT and molecular docking study

Gout is caused by hyperuricemia and has become the second largest metabolic disease in China after diabetes mellitus. Because xanthine oxidation (XOD) inhibitors represented by febuxostat, allopurinol, etc. have greater side effects, their clinical application is limited. In addition, the few types of these drugs limit the choice of patients. Previous studies have shown that as a class of potential XOD inhibitors, flavonoids have great development prospects. Because it can not only lower uric acid, but also reduce Reactive Oxygen Species (ROS). The influence of the substitution position and quantity of the hydroxyl group in flavonoids on the structure and properties of such compounds is one of the hotspots in medicinal chemistry research. This structural difference is also reflected in the inhibition of xanthine oxidase. In this study, monohydroxy flavone (MF) were used as a model, using quantum chemical calculations and molecular docking methods to study the structure, properties, antioxidant mechanisms and internal connections of ten compounds. The stability of MFs is improved when a hydroxyl group is introduced at the C5 position, and the substitution at the 2′and C6′ positions will reduce the stability of the compound. When there are hydroxyl groups at positions C5, C3, C6′ and C8, the B ring has a great degree of distortion. The presence of hydroxyl at C3 makes the flavonoids own good antioxidant activity. The hydroxyl group at the C7 position can penetrate deep into the active cavity and combine with the catalytic center, so that the compound can better exert its inhibitory effect. The research results can provide theoretical guidance for the development and upgrade of drugs for the treatment of hyperuricemia and gout.

Novel derivatives of aroylacrylic acid phenylamides as inducers of apoptosis through the ROS-mediated pathway in several cancer cell lines

In the present work, the α,β-double bond of the aroylacrylic acid phenylamides was suitably modified to optimize the toxicity–antiproliferative activity ratio of the resulting compounds 1–5. The phenylamides were modified by Michael's addition of suitably chosen piperidine-containing fragments: 1-amino-N-benzylpiperidine (a1), 4-benzylpiperidine (a2), and N,N-dimethyl-N-[2-(1-piperazinyl)-ethyl]amine (a3). The compounds exerted micromolar activity toward three cancer cell lines, A549, LoVo, and Skov-3, causing apoptotic cell death. It was shown that the nature of the cyclic amine moiety at position C2 of the compounds is probably the primary determinant of anticancer activity toward tested cell lines and the acute toxicity toward brine shrimp (Artemia salina). The majority of compounds revealed the ability to vigorously induce mitochondrial superoxide anion generation in all treated cell lines, which together with cell cycle arrest at the S phase and activation of intrinsic caspase cascade, indicates the possibility that apoptosis was triggered due to irreparable chromosomal damage by acute oxidative stress. Two derivatives also exerted significant antibacterial activity with one order of magnitude higher potency than chloramphenicol in most of the investigated bacterial strains. Also, the drug-like properties for all compounds were estimated by available software tools.