Polyamines mediate the inhibitory effect of drought stress on nitrogen reallocation and utilization to regulate grain number in wheat.

Drought stress poses a serious threat to grain formation in wheat. Nitrogen (N) plays crucial roles in plant organ development; however, the physiological mechanisms by which drought stress affects plant N availability and mediates the formation of grains in spikes of winter wheat are still unclear. In this study, we determined that pre-reproductive drought stress significantly reduced the number of fertile florets and the number of grains formed. Transcriptome analysis demonstrated that this was related to N metabolism, and in particular, the metabolism pathways of arginine (the main precursor for synthesis of polyamine) and proline. Continuous drought stress restricted plant N accumulation and reallocation rates, and plants preferentially allocated more N to spike development. As the activities of amino acid biosynthesis enzymes and catabolic enzymes were inhibited, more free amino acids accumulated in young spikes. The expression of polyamine synthase genes was down-regulated under drought stress, whilst expression of genes encoding catabolic enzymes was enhanced, resulting in reductions in endogenous spermidine and putrescine. Treatment with exogenous spermidine optimized N allocation in young spikes and leaves, which greatly alleviated the drought-induced reduction in the number of grains per spike. Overall, our results show that pre-reproductive drought stress affects wheat grain numbers by regulating N redistribution and polyamine metabolism.

Design and activity evaluation of new EGFR tyrosine kinase inhibitors containing cyclic polyamines.

The EGFR-TK pathway is pivotal in non-small-cell lung cancer (NSCLC) treatment, drugs targeting both EGFR wild-type and mutant tumor cells are still urgently needed. The focus of our study is on ATP-competitive inhibitors crucial for NSCLC therapy, specifically targeting the epidermal growth factor receptor (EGFR). A series of derivatives of Erlotinib and Icotinib were developed by incorporating a macrocyclic polyamine into a quinazoline scaffold to enhance their inhibitory activity against drug-resistant cells. The compounds exhibit modest activity against EGFR triple mutants (EGFRdel19/T790M/C797S). Compound b demonstrated slightly improved inhibition activity against PC-9del19/T790M/C797S (IC50 = 496.3 nM). This could provide some insights for optimizing EGFR inhibitors, particularly in the context of EGFR triple mutants.

Targeting c-Myc with decoy oligodeoxynucleotide-loaded polycationic nanoparticles inhibits cell growth and induces apoptosis in cancer stem-like cells (NTERA-2).

BACKGROUND: An increase in cancer stem cell (CSC) populations and their resistance to common treatments could be a result of c-Myc dysregulations in certain cancer cells. In the current study, we investigated anticancer effects of c-Myc decoy ODNs loaded-poly (methacrylic acid-co-diallyl dimethyl ammonium chloride) (PMA-DDA)-coated silica nanoparticles as carriers on cancer-like stem cells (NTERA-2). METHODS AND RESULTS: The physicochemical characteristics of the synthesized nanocomposites (SiO2@PMA-DDA-DEC) were analyzed using FT-IR, DLS, and SEM techniques. UV-Vis spectrophotometer was applied to analyze the release pattern of decoy ODNs from the nanocomposite. Furthermore, uptake, cell viability, apoptosis, and cell cycle assays were used to investigate the anticancer effects of nanocomposites loaded with c-Myc decoy ODNs on NTERA-2 cancer cells. The results of physicochemical analytics demonstrated that SiO2@PMA-DDA-DEC nanocomposites were successfully synthesized. The prepared nanocomposites were taken up by NTERA-2 cells with high efficiency, and could effectively inhibit cell growth and increase apoptosis rate in the treated cells compared to the control group. Moreover, SiO2@PMA-DDA nanocomposites loaded with c-Myc decoy ODNs induced cell cycle arrest at the G0/G1 phase in the treated cells. CONCLUSIONS: The conclusion drawn from this study is that c-Myc decoy ODN-loaded SiO2@PMA-DDA nanocomposites can effectively inhibit cell growth and induce apoptosis in NTERA-2 cancer cells. Moreover, given that a metal core is incorporated into this synthetic nanocomposite, it could potentially be used in conjunction with irradiation as part of a decoy-radiotherapy combinational therapy in future investigations.

Bachmann-Bupp syndrome and treatment.

Bachmann-Bupp syndrome (BABS) is a neurodevelopmental disorder characterized by developmental delay, hypotonia, and varying forms of non-congenital alopecia. The condition is caused by 3'-end mutations of the ornithine decarboxylase 1 (ODC1) gene, which produce carboxy (C)-terminally truncated variants of ODC, a pyridoxal 5'-phosphate-dependent enzyme. C-terminal truncation of ODC prevents its ubiquitin-independent proteasomal degradation and leads to cellular accumulation of ODC enzyme that remains catalytically active. ODC is the first rate-limiting enzyme that converts ornithine to putrescine in the polyamine pathway. Polyamines (putrescine, spermidine, spermine) are aliphatic molecules found in all forms of life and are important during embryogenesis, organogenesis, and tumorigenesis. BABS is an ultra-rare condition with few reported cases, but it serves as a convincing example for drug repurposing therapy. α-Difluoromethylornithine (DFMO, also known as eflornithine) is an ODC inhibitor with a strong safety profile in pediatric use for neuroblastoma and other cancers as well as West African sleeping sickness (trypanosomiasis). Patients with BABS have been treated with DFMO and have shown improvement in hair growth, muscle tone, and development.

Preventing Cancer by Inhibiting Ornithine Decarboxylase: A Comparative Perspective on Synthetic vs. Natural Drugs.

This perspective delves into the investigation of synthetic and naturally occurring inhibitors, their patterns of inhibition, and the effectiveness of newly utilized natural compounds as inhibitors targeting the Ornithine decarboxylase enzyme. This enzyme is known to target the MYC oncogene, thereby establishing a connection between polyamine metabolism and oncogenesis in both normal and cancerous cells. ODC activation and heightened polyamine activity are associated with tumor development in numerous cancers and fluctuations in ODC protein levels exert a profound influence on cellular activity for inhibition or suppressing tumor cells. This perspective outlines efforts to develop novel drugs, evaluate natural compounds, and identify promising inhibitors to address gaps in cancer prevention, highlighting the potential of newly designed synthetic moieties and natural flavonoids as alternatives. It also discusses natural compounds with potential as enhanced inhibitors.

Bactericidal Biodegradable Linear Polyamidoamines Obtained with the Use of Endogenous Polyamines.

The work presents the synthesis of a series of linear polyamidoamines by polycondensation of sebacoyl dichloride with endogenous polyamines: putrescine, spermidine, spermine, and norspermidine-a biogenic polyamine not found in the human body. During the synthesis carried out via interfacial reaction, hydrophilic, semi-crystalline polymers with an average viscosity molecular weight of approximately 20,000 g/mol and a melting point of approx. 130 °C were obtained. The structure and composition of the synthesized polymers were confirmed based on NMR and FTIR studies. The cytotoxicity tests performed on human fibroblasts and keratinocytes showed that the polymers obtained with spermine and norspermidine were strongly cytotoxic, but only in high concentrations. All the other examined polymers did not show cytotoxicity even at concentrations of 2000 µg/mL. Simultaneously, the antibacterial activity of the obtained polyamides was confirmed. These polymers are particularly active against E. Coli, and virtually all the polymers obtained demonstrated a strong inhibitory effect on the growth of cells of this strain. Antimicrobial activity of the tested polymer was found against strains like Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa. The broadest spectrum of bactericidal action was demonstrated by polyamidoamines obtained from spermine, which contains two amino groups in the repeating unit of the chain. The obtained polymers can be used as a material for forming drug carriers and other biologically active compounds in the form of micro- and nanoparticles, especially as a component of bactericidal creams and ointments used in dermatology or cosmetology.

Molecular Insights into the Synergistic Effects of Putrescine and Ammonium on Dinoflagellates.

Ammonium and polyamines are essential nitrogen metabolites in all living organisms. Crosstalk between ammonium and polyamines through their metabolic pathways has been demonstrated in plants and animals, while no research has been directed to explore this relationship in algae or to investigate the underlying molecular mechanisms. Previous research demonstrated that high concentrations of ammonium and putrescine were among the active substances in bacteria-derived algicide targeting dinoflagellates, suggesting that the biochemical inter-connection and/or interaction of these nitrogen compounds play an essential role in controlling these ecologically important algal species. In this research, putrescine, ammonium, or a combination of putrescine and ammonium was added to cultures of three dinoflagellate species to explore their effects. The results demonstrated the dose-dependent and species-specific synergistic effects of putrescine and ammonium on these species. To further explore the molecular mechanisms behind the synergistic effects, transcriptome analysis was conducted on dinoflagellate Karlodinium veneficum treated with putrescine or ammonium vs. a combination of putrescine and ammonium. The results suggested that the synergistic effects of putrescine and ammonium disrupted polyamine homeostasis and reduced ammonium tolerance, which may have contributed to the cell death of K. veneficum. There was also transcriptomic evidence of damage to chloroplasts and impaired photosynthesis of K. veneficum. This research illustrates the molecular mechanisms underlying the synergistic effects of the major nitrogen metabolites, ammonium and putrescine, in dinoflagellates and provides direction for future studies on polyamine biology in algal species.

Sensing and Microbiological Activity of a New Blue Fluorescence Polyamidoamine Dendrimer Modified with 1,8-Naphthalimide Units.

A novel second-generation blue fluorescent polyamidoamine dendrimer peripherally modified with sixteen 4-N,N-dimethylaninoethyloxy-1,8-naphthalimide units was synthesized. Its basic photophysical characteristics were investigated in organic solvents of different polarity. It was found that in these solvents, the dendrimer is colorless and emitted blue fluorescence with different intensities depending on their polarity. The effect of the pH of the medium on the fluorescence intensity was investigated and it was found that in the acidic medium, the fluorescence is intense and is quenched in the alkaline medium. The ability of the dendrimer to detect metal ions (Pb2+, Zn2+, Mg2+, Sn2+, Ba2+, Ni2+, Sn2+, Mn2+, Co2+, Fe3+, and Al3+) was also investigated, and it was found that in the presence of Fe3+, the fluorescent intensity was amplified more than 66 times. The antimicrobial activity of the new compound has been tested in vitro against Gram-positive B. cereus and Gram-negative P. aeruginosa. The tests were performed in the dark and after irradiation with visible light. The antimicrobial activity of the compound enhanced after light irradiation and B. cereus was found slightly more sensitive than P. aeruginosa. The increase in antimicrobial activity after light irradiation is due to the generation of singlet oxygen particles, which attack bacterial cell membranes.

Flexure wood formation via growth reprogramming in hybrid aspen involves jasmonates and polyamines and transcriptional changes resembling tension wood development.

Stem bending in trees induces flexure wood but its properties and development are poorly understood. Here, we investigated the effects of low-intensity multidirectional stem flexing on growth and wood properties of hybrid aspen, and on its transcriptomic and hormonal responses. Glasshouse-grown trees were either kept stationary or subjected to several daily shakes for 5 wk, after which the transcriptomes and hormones were analyzed in the cambial region and developing wood tissues, and the wood properties were analyzed by physical, chemical and microscopy techniques. Shaking increased primary and secondary growth and altered wood differentiation by stimulating gelatinous-fiber formation, reducing secondary wall thickness, changing matrix polysaccharides and increasing cellulose, G- and H-lignin contents, cell wall porosity and saccharification yields. Wood-forming tissues exhibited elevated jasmonate, polyamine, ethylene and brassinosteroids and reduced abscisic acid and gibberellin signaling. Transcriptional responses resembled those during tension wood formation but not opposite wood formation and revealed several thigmomorphogenesis-related genes as well as novel gene networks including FLA and XTH genes encoding plasma membrane-bound proteins. Low-intensity stem flexing stimulates growth and induces wood having improved biorefinery properties through molecular and hormonal pathways similar to thigmomorphogenesis in herbaceous plants and largely overlapping with the tension wood program of hardwoods.

Polyamines: their significance for maintaining health and contributing to diseases.

Polyamines are essential for the growth and proliferation of mammalian cells and are intimately involved in biological mechanisms such as DNA replication, RNA transcription, protein synthesis, and post-translational modification. These mechanisms regulate cellular proliferation, differentiation, programmed cell death, and the formation of tumors. Several studies have confirmed the positive effect of polyamines on the maintenance of health, while others have demonstrated that their activity may promote the occurrence and progression of diseases. This review examines a variety of topics, such as polyamine source and metabolism, including metabolism, transport, and the potential impact of polyamines on health and disease. In addition, a brief summary of the effects of oncogenes and signaling pathways on tumor polyamine metabolism is provided. Video Abstract.

Noncovalent Bile Acid Oligomers as Facial Amphiphilic Antimicrobials.

New antimicrobial agents are needed to address the ever-growing risk of bacterial resistance, particularly for methicillin- and vancomycin-resistant Staphylococcus aureus (S. aureus). Here, we report a class of bile acid oligomers as facial amphiphilic antimicrobials, which are noncovalently fabricated by cholic acid (CA) and deoxycholic acid (DCA) with polyamines (e.g., diamines, diethylenetriamine, spermidine, and spermine). The antibacterial activities of these bile acid oligomers (CA/polyamines and DCA/polyamines) against S. aureus become stronger with increasing the amine group numbers of polyamines without obviously enhanced cytotoxicity and skin irritation. DCA/spermine, entirely composed of natural products, exhibits the best antibacterial activity but the lowest cytotoxicity and the weakest skin irritation. All CA/polyamines and DCA/polyamines form well-ordered ribbon-like aggregates, collecting numerous facial amphiphilic structures to significantly enhance the interactions with bacterial membranes. In particular, the biogenic polyamines with more than two amine groups provide extra positively charged sites, hence facilitating the binding of bile acid oligomers to the negatively charged outer membrane of the bacteria via electrostatic interaction. This in turn promotes more oligomeric bile acid units that can be inserted into the membrane through hydrophobic interaction between bile acids and lipid domains. The noncovalently constructed and separable amphiphilic antimicrobials can avoid the long-term coexistence of microorganisms and antibacterial molecules in different acting modes. Therefore, the noncovalent bile acid oligomers, especially those with higher oligomerization degrees, can be a potential approach to effectively enhance antibacterial activity, improve environmental friendliness, and reduce bacterial drug resistance.

Amphiphilic Polyamine α-Synuclein Aggregation Inhibitors from the Sponge Aaptos lobata.

Bioassay-guided investigation of the sponge Aaptos lobata resulted in the isolation and identification of two new amphiphilic polyamines, aaptolobamines A (1) and B (2). Their structures were determined through analysis of NMR and MS data. MS analysis also indicated that A. lobata contained a complex mixture of aaptolobamine homologues. Both aaptolobamines A (1) and B (2) show broad bioactivity, including cytotoxicity against cancer cell lines, moderate antimicrobial activity against a methicillin-resistant strain of Staphylococcus aureus, and weak activity against a Pseudomonas aeruginosa strain. The mixtures of aaptolobamine homologues were shown to contain compounds that bind to the Parkinson's disease associated amyloid protein α-synuclein and inhibit its aggregation.

Enhanced cell growth, production, and mAb quality produced in Chinese hamster ovary-K1 cells by supplementing polyamine in the media.

Polyamines such as putrescine (PUT), spermidine (SPD), and spermine (SPM) are amine group-containing biomolecules that regulate multiple intracellular functions such as proliferation, differentiation, and stress response in mammalian cells. Although these biomolecules can be generated intracellularly, lack of polyamine-synthesizing activity has occasionally been reported in a few mammalian cell lines such as Chinese hamster ovary (CHO)-K1; thus, polyamine supplementation in serum-free media is required to support cell growth and production. In the present study, the effects of biogenic polyamines PUT, SPD, and SPM in media on cell growth, production, metabolism, and antibody quality were explored in cultures of antibody-producing CHO-K1 cells. Polyamine withdrawal from media significantly suppressed cell growth and production. On the other hand, enhanced culture performance was achieved in polyamine-containing media conditions in a dose-dependent manner regardless of polyamine type. In addition, in polyamine-deprived medium, distinguishing metabolic features, such as enriched glycolysis and suppressed amino acid consumption, were observed and accompanied by higher heterogeneity of antibody quality compared with the optimal concentration of polyamines. Furthermore, an excessive concentration of polyamines negatively affected culture performance as well as antibody quality. Hence, the results suggest that polyamine-related metabolism needs to be further investigated and polyamines in cell growth media should be optimized as a controllable parameter in CHO cell culture bioprocessing. KEY POINTS: • Polyamine supplementation enhanced cell growth and production in a dose-dependent manner • Polyamine type and concentration in the media affected mAb quality • Optimizing polyamines in the media is suggested in CHO cell bioprocessing.

TGase-induced Cd tolerance by boosting polyamine, nitric oxide, cell wall composition and phytochelatin synthesis in tomato.

In highly intensive greenhouse vegetable production, soil acidification was caused by excessive fertilization, increasing cadmium (Cd) concentrations in the vegetables, which bears environmental hazards and is a negative influence on vegetables and humans. Transglutaminases (TGases), a central mediator for certain physiological effects of polyamines (PAs) in the plant kingdom, play important roles in plant development and stress response. Despite increased research on the crucial role of TGase in protecting against environmental stresses, relatively little is known about the mechanisms of Cd tolerance. In this study, we found, TGase activity and transcript level, which was upregulated by Cd, and TGase-induced Cd tolerance related to endogenous bound PAs increase and formation of nitric oxide (NO). Plant growth of tgase mutants was hypersensitive to Cd, chemical complementation by putrescine, sodium nitroprusside (SNP, nitric oxide donor) or gain of function TGase experiments restore Cd tolerance. α-diflouromethylornithine (DFMO, a selective ODC inhibitor) and 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO, NO scavenger), were respectively found declined drastically endogenous bound PA and NO content in TGase overexpression plants. Likewise, we reported that TGase interacted with polyamine uptake protein 3 (Put3), and the silencing of Put3 largely reduced TGase-induced Cd tolerance and bound PAs formation. This salvage strategy depends on TGase-regulated synthesis of bound PAs and NO that is able to positively increase the concentration of thiol and phytochelatins, elevate Cd in the cell wall, as well as induce the levels of expression Cd uptake and transport genes. Collectively, these findings indicate that TGase-mediated enhanced levels of bound PA and NO acts as a vital mechanism to protect the plant from Cd-caused toxicity.

α,ω-Diacyl-Substituted Analogues of Natural and Unnatural Polyamines: Identification of Potent Bactericides That Selectively Target Bacterial Membranes.

In this study, α-ω-disubstituted polyamines exhibit a range of potentially useful biological activities, including antimicrobial and antibiotic potentiation properties. We have prepared an expanded set of diarylbis(thioureido)polyamines that vary in central polyamine core length, identifying analogues with potent methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, Acinetobacter baumannii and Candida albicans growth inhibition properties, in addition to the ability to enhance action of doxycycline towards Gram-negative bacterium Pseudomonas aeruginosa. The observation of associated cytotoxicity/hemolytic properties prompted synthesis of an alternative series of diacylpolyamines that explored aromatic head groups of varying lipophilicity. Examples bearing terminal groups each containing two phenyl rings (15a-f, 16a-f) were found to have optimal intrinsic antimicrobial properties, with MRSA being the most susceptible organism. A lack of observed cytotoxicity or hemolytic properties for all but the longest polyamine chain variants identified these as non-toxic Gram-positive antimicrobials worthy of further study. Analogues bearing either one or three aromatic-ring-containing head groups were either generally devoid of antimicrobial properties (one ring) or cytotoxic/hemolytic (three rings), defining a rather narrow range of head group lipophilicity that affords selectivity for Gram-positive bacterial membranes versus mammalian. Analogue 15d is bactericidal and targets the Gram-positive bacterial membrane.

Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors.

S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes.

Polyamine-Drug Conjugates: Do They Boost Drug Activity?

Over the past two decades, the strategy of conjugating polyamine tails with bioactive molecules such as anticancer and antimicrobial agents, as well as antioxidant and neuroprotective scaffolds, has been widely exploited to enhance their pharmacological profile. Polyamine transport is elevated in many pathological conditions, suggesting that the polyamine portion could improve cellular and subcellular uptake of the conjugate via the polyamine transporter system. In this review, we have presented a glimpse on the polyamine conjugate scenario, classified by therapeutic area, of the last decade with the aim of highlighting achievements and fostering future developments.

From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs.

Monoamine oxidases (MAOs) are well-known pharmacological targets in neurological and neurodegenerative diseases. However, recent studies have revealed a new role for MAOs in certain types of cancer such as glioblastoma and prostate cancer, in which they have been found overexpressed. This finding is opening new frontiers for MAO inhibitors as potential antiproliferative agents. In light of our previous studies demonstrating how a polyamine scaffold can act as MAO inhibitor, our aim was to search for novel analogs with greater inhibitory potency for human MAOs and possibly with antiproliferative activity. A small in-house library of polyamine analogs (2-7) was selected to investigate the effect of constrained linkers between the inner amine functions of a polyamine backbone on the inhibitory potency. Compounds 4 and 5, characterized by a dianiline (4) or dianilide (5) moiety, emerged as the most potent, reversible, and mainly competitive MAO inhibitors (Ki < 1 µM). Additionally, they exhibited a high antiproliferative activity in the LN-229 human glioblastoma cell line (GI50 < 1 µM). The scaffold of compound 5 could represent a potential starting point for future development of anticancer agents endowed with MAO inhibitory activity.

An Undefined Interaction between Polyamines and Heat Shock Proteins Leads to Cellular Protection in Plasmodium falciparum and Proliferating Cells in Various Organisms.

Environmental stimuli can distress the internal reaction of cells and their normal function. To react promptly to sudden environmental changes, a cascade of heat shock proteins (Hsps) functions to protect and act as housekeepers inside the cells. In parallel to the heat shock response, the metabolic polyamine (PA) status changes. Here, we discuss possible ways of putative interactions between Hsps and polyamines in a wide lineage of eukaryotic model organisms with a particular focus on parasitic protozoa such as Plasmodium falciparum (P. falciparum). The supposed interaction between polyamines and Hsps may protect the parasite from the sudden change in temperature during transmission from the female Anopheles mosquito to a human host. Recent experiments performed with the spermidine mimetic inhibitor 15-deoxyspergualine in Plasmodium in vitro cultures show that the drug binds to the C-terminal EEVD motif of Hsp70. This leads to inhibition of protein biosynthesis caused by prevention of eIF5A2 phosphorylation and eukaryotic initiation factor 5A (eIF5A) modification. These observations provide further evidence that PAs are involved in the regulation of protein biosynthesis of Hsps to achieve a protective effect for the parasite during transmission.

Antimicrobial Properties of New Polyamines Conjugated with Oxygen-Containing Aromatic Functional Groups.

Antibiotic resistance is now a first-order health problem, which makes the development of new families of antimicrobials imperative. These compounds should ideally be inexpensive, readily available, highly active, and non-toxic. Here, we present the results of our investigation regarding the antimicrobial activity of a series of natural and synthetic polyamines with different architectures (linear, tripodal, and macrocyclic) and their derivatives with the oxygen-containing aromatic functional groups 1,3-benzodioxol, ortho/para phenol, or 2,3-dihydrobenzofuran. The new compounds were prepared through an inexpensive process, and their activity was tested against selected strains of yeast, as well as Gram-positive and Gram-negative bacteria. In all cases, the conjugated derivatives showed antimicrobial activity higher than the unsubstituted polyamines. Several factors, such as the overall charge at physiological pH, lipophilicity, and the topology of the polyamine scaffold were relevant to their activity. The nature of the lipophilic moiety was also a determinant of human cell toxicity. The lead compounds were found to be bactericidal and fungistatic, and they were synergic with the commercial antifungals fluconazole, cycloheximide, and amphotericin B against the yeast strains tested.