Cocatalytic Activity of the Furfuryl and Oxanorbornane-Substituted Guanidines in the Aldol Reaction Catalyzed by (S)-Proline.

This work investigated the cocatalytic activity of recently prepared guanidinium salts containing an oxanorbornane subunit in an (S)-proline-catalyzed aldol reaction. The activity was interpreted by the diastereoselectivity of the reaction (anti/syn ratio) and for the most interesting polycyclic guanidinium salt, the enantioselectivity of the reaction was determined. The results indicated a negative impact on the oxanorbornane unit if present as the flexible substituent. For most of the tested aldehydes, the best cocatalysts provided enantioselectivities above 90% and above 95% at room temperature and 0 °C, respectively, culminating in >99.5% for 4-chloro- and 2-nitrobenzaldehyde as the substrate. The barriers for forming four possible enantiomers were calculated and the results for two anti-enantiomers are qualitatively consistent with the experiment. Obtained results suggest that the representatives of furfurylguanidinium and rigid polycyclic oxanorbornane-substituted guanidinium salts are good lead structures for developing new cocatalysts by tuning the chemical space around the guanidine moiety.

Aptamer-based biosensors for the detection of neonicotinoid insecticides in environmental samples: A systematic review.

Neonicotinoids, sometimes abbreviated as neonics, represent a class of neuro-active insecticides with chemical similarities to nicotine. Neonicotinoids are the most widely adopted group of insecticides globally since their discovery in the late 1980s. Their physiochemical properties surpass those of previously established insecticides, contributing to their popularity in various sectors such as agriculture and wood treatment. The environmental impact of neonicotinoids, often overlooked, underscores the urgency to develop tools for their detection and understanding of their behavior. Conventional methods for pesticide detection have limitations. Chromatographic techniques are sensitive but expensive, generate waste, and require complex sample preparation. Bioassays lack specificity and accuracy, making them suitable as preliminary tests in conjunction with instrumental methods. Aptamer-based biosensor is recognized as an advantageous tool for neonicotinoids detection due to its rapid response, user-friendly nature, cost-effectiveness, and suitability for on-site detection. This comprehensive review represents the inaugural in-depth analysis of advancements in aptamer-based biosensors targeting neonicotinoids such as imidacloprid, thiamethoxam, clothianidin, acetamiprid, thiacloprid, nitenpyram, and dinotefuran. Additionally, the review offers valuable insights into the critical challenges requiring prompt attention for the successful transition from research to practical field applications.

Novel Sulfoximine Derivatives Containing Cyanoguanidine and Nitroguanidine Moieties: Design, Synthesis, and Bioactivities.

A total of 32 novel sulfoximines bearing cyanoguanidine and nitroguanidine moieties were designed and synthesized by a rational molecule design strategy. The bioactivities of the title compounds were evaluated and the results revealed that some of the target compounds possessed excellent antifungal activities against six agricultural fungi, including Sclerotinia sclerotiorum, Fusarium graminearum, Phytophthora capsici, Botrytis cinerea, Rhizoctonia solani, and Pyricularia grisea. Among them, compounds 8e1 and 8e4 exhibited significant efficacy against P. grisea with EC50 values of 2.72 and 2.98 µg/mL, respectively, which were much higher than that of commercial fungicides boscalid (47.95 µg/mL). Interestingly, in vivo assays determined compound 8e1 possessed outstanding activity against S. sclerotiorum with protective and curative effectiveness of 98 and 95.6% at 50 µg/mL, which were comparable to those of boscalid (93.2, 91.9%). The further preliminary mechanism investigation disclosed that compound 8e1 could damage the structure of the cell membrane of S. sclerotiorum, increase its permeability, and suppress its growth. Overall, the findings enhanced that these novel sulfoximine derivatives could be potential lead compounds for the development of new fungicides.

Collection and transportation of SARS-CoV-2 and influenza A virus diagnostic samples: Optimizing the usage of guanidine-based chaotropic salts for enhanced biosafety and viral genome preservation.

Many virus lysis/transport buffers used in molecular diagnostics, including the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, contain guanidine-based chaotropic salts, primarily guanidine hydrochloride (GuHCl) or guanidine isothiocyanate (GITC). Although the virucidal effects of GuHCl and GITC alone against some enveloped viruses have been established, standardized data on their optimum virucidal concentrations against SARS-CoV-2 and effects on viral RNA stability are scarce. Thus, we aimed to determine the optimum virucidal concentrations of GuHCl and GITC against SARS-CoV-2 compared to influenza A virus (IAV), another enveloped respiratory virus. We also evaluated the effectiveness of viral RNA stabilization at the determined optimum virucidal concentrations under high-temperature conditions (35°C) using virus-specific real-time reverse transcription polymerase chain reaction. Both viruses were potently inactivated by 1.0 M GITC and 2.5 M GuHCl, but the GuHCl concentration for efficient SARS-CoV-2 inactivation was slightly higher than that for IAV inactivation. GITC showed better viral RNA stability than GuHCl at the optimum virucidal concentrations. An increased concentration of GuHCl or GITC increased viral RNA degradation at 35°C. Our findings highlight the need to standardize GuHCl and GITC concentrations in virus lysis/transport buffers and the potential application of these guanidine-based salts alone as virus inactivation solutions in SARS-CoV-2 and IAV molecular diagnostics.

Effect of the Phosphoryl Guanidine Modification in Chimeric DNA-RNA crRNAs on the Activity of the CRISPR-Cas9 System In Vitro.

Currently, the CRISPR-Cas9 system serves as a prevalent tool for genome editing and gene expression regulation. Its therapeutic application is limited by off-target effects that can affect genomic integrity through nonspecific, undesirable changes in the genome. Various strategies have been explored to mitigate the off-target effects. Many approaches focus on modifying components of the system, namely, Cas9 and guide RNAs, to enhance specificity. However, a common challenge is that methods aiming to increase specificity often result in a significant reduction in the editing efficiency. Here, we introduce a novel approach to modifying crRNA to balance CRISPR-Cas9 specificity and efficiency. Our approach involves incorporating nucleoside modifications, such as replacing ribo- to deoxyribonucleosides and backbone modifications, using phosphoryl guanidine groups, specifically 1,3-dimethylimidazolidin-2-ylidene phosphoramidate. In this case, within the first 10 nucleotides from the 5' crRNA end, phosphodiester bonds are substituted with phosphoryl guanidine groups. We demonstrate that crRNAs containing a combination of deoxyribonucleosides and single or multiple phosphoryl guanidine groups facilitate the modulation of CRISPR-Cas9 system activity while improving its specificity in vitro.

Effectively adsorb Au(S2O3)23- using aminoguanidine as trapping group from thiosulfate solutions.

Thiosulfate gold leaching is one of the most promising green cyanide-free gold extraction processes; however, the difficulty of recovering Au(I) from the leaching system hinders its further development. This study prepared aminoguanidine-functionalized microspheres (AGMs) via a one-step reaction involving nucleophilic substitution between aminoguanidine hydrochloride and chloromethylated polystyrene microspheres and used AGMs to adsorb Au(I) from thiosulfate solutions. Scanning electron microscopy, Brunauer-Emmett-Teller analysis, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy were used to analyze the structure and properties of AGMs. Experiments were designed to investigate the effects of pH, temperature, initial Au(I), and thiosulfate concentrations on the gold adsorption performance of AGMs. Results demonstrated that AGMs can efficiently adsorb Au(I) from thiosulfate solutions in a wide pH range. The adsorption process conforms to the pseudo-second-order kinetic model and Langmuir isotherm model, with a maximum capacity of 22.03 kg/t. Acidic thiourea is an effective desorbent, and after four adsorption-desorption cycles, the adsorption rate of Au(I) by AGMs is 78.63%, which shows AGMs have good cyclic application potential. Based on the results of characterization, experiments, and density functional theory calculations, the mechanism for the adsorption of [Au(S2O3)2]3- on AGMs involves anion exchange. Importantly, AGMs exhibited satisfactory adsorption property for Au(I) in practical Cu2+-NH3(en)-S2O32- systems. This study provided experimental reference for the recovery of Au(I) from thiosulfate solution.

Assessing the potential of nano-formulated chlorfenapyr and clothianidin insecticides-treated sugar baits against Anopheles funestus, Anopeles coluzzii and Culex quinquefasciatus mosquitoes.

Mosquitoes serve as vectors for various diseases like malaria, dengue fever, yellow fever, and lymphatic filarial diseases causing significant global health problems, highlighting the importance of vector control. The study was conducted to assess the effectiveness of nanoformulated clothianidin and chlorfenapyr insecticides treated with ATSB in controlling three mosquito strains. The development of a natural thiolated polymer-coated ATSB nano formulation involved incorporating nano-carriers to deliver insecticides. Field- collected mosquito strains were subjected to laboratory-based bioassays using 1 % and 1.5 % concentrations of each conventionally used and nanoformulated insecticide with ATSB solution. Adult mosquitoes were left overnight to contact with N-ATSB and efficacy was recorded after 36 and 72 h. The results showed that nanoformulated chlorfenapyr was significantly more effective as compared to clothianidin against An. funestus and Cx. quinquefasciatus but the results were not significantly different against An. coluzzii (100 %). An. coluzzii was found to be the most susceptible strain followed by An. funestus and showed 100 % and ∼ 98 % mortality against nanoformulated chlorfenapyr (1.5 %). Nanoformulated clothianidin induced more than 92 % and ∼ 100 % mortality against An. funestus and An. coluzzii respectively. However, Cx. quinquefasciatus significantly showed less mortality against nanoformulated clothianidin (88 %) and chlorfenapyr (>95 %) as compared to Anopheline strains. Furthermore, results indicate that nanoformulated insecticides significantly caused greater and prolonged fatality as compared to conventional form, suggesting effective and suitable strategies for vector management.

Cellulose aerogel beads and monoliths from CO2-based reversible ionic liquid solution.

The CO2-based reversible ionic liquid solution of 1,1,3,3-tetramethylguanidine (TMG) and ethylene glycol (EG) in dimethyl sulfoxide (DMSO) after capturing CO2, (2[TMGH]+[O2COCH2CH2OCO2]2-/DMSO (χRILs = 0.1), provides a sustainable and effective platform for cellulose dissolution and homogeneous utilization. Highly porous cellulose aerogel beads and monoliths were successfully prepared via a sol-gel process by extruding cellulose solution into different coagulation baths (NaOH aqueous solution or alcohols) and exposing the cellulose solution in open environment, respectively, and followed by different drying techniques, including supercritical CO2-drying, freeze-drying and air-drying. The effect of the coagulation baths and drying protocols on the multi-scale structure of the as-prepared cellulose aerogel beads and monoliths were studied in detail, and the sol-gel transition mechanism was also studied by the solvatochromic parameters determination. High specific surface area of 252 and 207 m2/g for aerogel beads and monoliths were achieved, respectively. The potential of cellulose aerogels in dye adsorption was demonstrated.

Ion-imprinted aminoguanidine-chitosan for selective recognition of lanthanum (III) from wastewater.

Developing a sorbent for the removal of La3+ ions from wastewater offers significant environmental and economic advantages. This study employed an ion-imprinting process to integrate La3+ ions into a newly developed derivative of aminoguanidine-chitosan (AGCS), synthesized via an innovative method. The process initiated with the modification of chitosan by attaching cyanoacetyl groups through amide bonds, yielding cyanoacetyl chitosan (CAC). This derivative underwent further modification with aminoguanidine to produce the chelating AGCS biopolymer. The binding of La3+ ions to AGCS occurred through imprinting and cross-linking with epichlorohydrin (ECH), followed by the extraction of La3+, resulting in the La3+ ion-imprinted sorbent (La-AGCS). Structural confirmation of these chitosan derivatives was established through elemental analysis, FTIR, and NMR. SEM analysis revealed that La-AGCS exhibited a more porous structure compared to the smoother non-imprinted polymer (NIP). La-AGCS demonstrated superior La3+ capture capability, with a maximum capacity of 286 ± 1 mg/g. The adsorption process, fitting the Langmuir and pseudo-second-order models, indicated a primary chemisorption mechanism. Moreover, La-AGCS displayed excellent selectivity for La3+, exhibiting selectivity coefficients ranging from 4 to 13 against other metals. This study underscores a strategic approach in designing advanced materials tailored for La3+ removal, capitalizing on specific chelator properties and ion-imprinting technology.

RNA Isolation Method in Marginal Crops with High Agronomic Potential.

Ribonucleic Acid (RNA) isolation is a basic technique in the field of molecular biology. The purpose of RNA isolation is to acquire pure and complete RNA that can be used to evaluate gene expression. Many methods can be used to perform RNA isolation, all of them based on the chemical properties of nucleic acids. However, some of them do not achieve high RNA yields and purity levels when used in a number of marginally studied crops of agronomic importance, such as grain and vegetable amaranth plants. In the method described here, the use of guanidinium thiocyanate and two additional precipitation steps with different reagents designed to obtain high yields and RNA purity levels from diverse plant species employed for plant functional genomics studies is described.

Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities.

Mellpaladines A-C (1-3) and dopargimine (4) are dopamine-derived guanidine alkaloids isolated from a specimen of Palauan Didemnidae tunicate as possible modulators of neuronal receptors. In this study, we isolated the dopargimine derivative 1-carboxydopargimine (5), three additional mellpaladines D-F (6-8), and serotodopalgimine (9), along with a dimer of serotonin, 5,5'-dihydroxy-4,4'-bistryptamine (10). The structures of these compounds were determined based on spectrometric and spectroscopic analyses. Compound 4 and its congeners dopargine (11), nordopargimine (15), and 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)ethan-1-amine (16) were synthetically prepared for biological evaluations. The biological activities of all isolated compounds were evaluated in comparison with those of 1-4 using a mouse behavioral assay upon intracerebroventricular injection, revealing key functional groups in the dopargimines and mellpaladines for in vivo behavioral toxicity. Interestingly, these alkaloids also emerged during a screen of our marine natural product library aimed at identifying antiviral activities against dengue virus, SARS-CoV-2, and vesicular stomatitis Indiana virus (VSV) pseudotyped with Ebola virus glycoprotein (VSV-ZGP).

A Guanidinobenzol-Rich Polymer Overcoming Cascade Delivery Barriers for CRISPR-Cas9 Genome Editing.

The efficient cytosolic delivery of the CRISPR-Cas9 machinery remains a challenge for genome editing. Herein, we performed ligand screening and identified a guanidinobenzol-rich polymer to overcome the cascade delivery barriers of CRISPR-Cas9 ribonucleoproteins (RNPs) for genome editing. RNPs were stably loaded into the polymeric nanoparticles (PGBA NPs) by their inherent affinity. The polymer facilitated rapid endosomal escape of RNPs via a dynamic multiple-step cascade process. Importantly, the incorporation of fluorescence in the polymer helps to identify the correlation between cellular uptake and editing efficiency, increasing the efficiency up to 70% from the initial 30% for the enrichment of edited cells. The PGBA NPs efficiently deliver RNPs for in vivo gene editing via both local and systemic injections and dramatically reduce PCSK9 level. These results indicate that PGBA NPs enable the cascade delivery of RNPs for genome editing, showing great promise in broadening the therapeutic potential of the CRISPR-Cas9 technique.

Exploring the neurotoxicity of chiral dinotefuran towards nicotinic acetylcholine receptors: Enantioselective insights into species selectivity.

Dinotefuran is a chiral neonicotinoid that is widely distributed in environmental matrices, but its health risks to different organisms are poorly understood. This study investigated the neurotoxic responses of honeybee/cotton aphid nicotinic acetylcholine receptors (nAChRs) to chiral dinotefuran at the enantiomeric scale and demonstrated the microscopic mechanism of species selectivity in nAChR-mediated enantioselective neurotoxicity. The findings indicated that (S)-dinotefuran had a higher affinity for honeybee nAChR than (R)-dinotefuran whereas both enantiomers exhibited similar bioactivity toward cotton aphid nAChR. The results of dynamic neurotoxic processes indicated the association of conformational changes induced by chiral dinotefuran with its macroscopic neurotoxicity, and (R)-dinotefuran, which exhibit low toxicity to honeybee, was found to induce significant conformational changes in the enantioselective neurotoxic reaction, as supported by the average root-mean-square fluctuation (0.35 nm). Energy decomposition results indicated that electrostatic contribution (ΔGele) is the critical energy term that leads to substantial enantioselectivity, and both Trp-51 (－2.57 kcal mol-1) and Arg-75 (－4.86 kcal mol-1), which form a hydrogen-bond network, are crucial residues in mediating the species selectivity for enantioselective neurotoxic responses. Clearly, this study provides experimental evidence for a comprehensive assessment of the health hazards of chiral dinotefuran.

Biodegradable Lipid-Modified Poly(Guanidine Thioctic Acid)s: A Fortifier of Lipid Nanoparticles to Promote the Efficacy and Safety of mRNA Cancer Vaccines.

Lipid nanoparticles (LNPs)-based messenger RNA (mRNA) therapeutics have emerged with promising potentials in the fields of infectious diseases, cancer vaccines, and protein replacement therapies; however, their therapeutic efficacy and safety can still be promoted by the optimization of LNPs formulations. Unfortunately, current LNPs suffer from increased production of reactive oxygen species during translation, which leads to a decreased translation efficiency and the onset of inflammation and other side effects. Herein, we synthesize a lipid-modified poly(guanidine thioctic acid) polymer to fabricate novel LNPs for mRNA vaccines. The acquired G-LNPs significantly promote the translation efficiency of loaded mRNA and attenuate inflammation after vaccination through the elimination of reactive oxygen species that are responsible for translational inhibition and inflammatory responses. In vivo studies demonstrate the excellent antitumor efficacy of the G-LNPs@mRNA vaccine, and two-dose vaccination dramatically increases the population and infiltration of cytotoxic T cells due to the intense antitumor immune responses, thus generating superior antitumor outcomes compared with the mRNA vaccine prepared from traditional LNPs. By synergy with immune checkpoint blockade, the tumor inhibition of G-LNPs@mRNA is further boosted, indicating that G-LNPs-based mRNA vaccines will be powerful and versatile platforms to combat cancer.

Highly Concentrated Linear Guanidine Amides from the Marine Sipunculid Phascolosoma granulatum.

The chemical diversity of annelids, particularly those belonging to the class Sipuncula, remains largely unexplored. However, as part of a Marine Biodiscovery program in Ireland, the peanut worm Phascolosoma granulatum emerged as a promising source of unique metabolites. The purification of the MeOH/CH2Cl2 extract of this species led to the isolation of six new linear guanidine amides, named phascolosomines A-F (1-6). NMR analysis allowed for the elucidation of their structures, all of which feature a terminal guanidine, central amide linkage, and a terminal isobutyl group. Notably, these guanidine amides were present in unusually high concentrations, comprising ∼3% of the dry mass of the organism. The primary concentration of the phascolosomines in the viscera is similar to that previously identified in linear amides from sipunculid worms and marine fireworms. The compounds from sipunculid worms have been hypothesized to be toxins, while those from fireworms are reported to be defensive irritants. However, screening of the newly isolated compounds for inhibitory bioactivity showed no significant inhibition in any of the assays conducted.

Adsorption of CMIT/MIT on the Model Pulmonary Surfactant Monolayers.

Polyhexamethylene guanidine (PHMG) is a guanidine-based chemical that has long been used as an antimicrobial agent. However, recently raised concerns regarding the pulmonary toxicity of PHMG in humans and aquatic organisms have led to research in this area. Along with PHMG, there are concerns about the safety of non-guanidine 5-chloro-2-methylisothiazol-3(2H)-one/2-methylisothiazol-3(2H)-one (CMIT/MIT) in human lungs; however, the safety of such chemicals can be affected by many factors, and it is difficult to rationalize their toxicity. In this study, we investigated the adsorption characteristics of CMIT/ MIT on a model pulmonary surfactant (lung surfactant, LS) using a Langmuir trough attached to a fluorescence microscope. Analysis of the π-A isotherms and lipid raft morphology revealed that CMIT/MIT exhibited minimal adsorption onto the LS monolayer deposited at the air/water interface. Meanwhile, PHMG showed clear signs of adsorption to LS, as manifested by the acceleration of the L o phase growth with increasing surface pressure. Consequently, in the presence of CMIT/MIT, the interfacial properties of the model LS monolayer exhibited significantly fewer changes than PHMG.

Antimicrobial Guanidinylate Polycarbonates Show Oral In Vivo Efficacy Against Clostridioides Difficile.

The emerging antibiotic resistance has been named by the World Health Organization (WHO) as one of the top 10 threats to public health. Notably, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VREF) are designated as serious threats, whereas Clostridioides difficile (C. difficile) is recognized as one of the most urgent threats to human health and unmet medical need. Herein, they report the design and application of novel biodegradable polymers - the lipidated antimicrobial guanidinylate polycarbonates. These polymers showed potent antimicrobial activity against a panel of bacteria with fast-killing kinetics and low resistance development tendency, mainly due to their bacterial membrane disruption mechanism. More importantly, the optimal polymer showed excellent antibacterial activity against C. difficile infection (CDI) in vivo via oral administration. In addition, compared with vancomycin, the polymer demonstrated a much-prolonged therapeutic effect and virtually diminished recurrence rate of CDI. The convenient synthesis, easy scale-up, low cost, as well as biodegradability of this class of polycarbonates, together with their in vitro broad-spectrum antimicrobial activity and orally in vivo efficacy against CDI, suggest the great potential of lipidated guandinylate polycarbonates as a new class of antibacterial biomaterials to treat CDI and combat emerging antibiotic resistance.

Mechanism of the extremely high duplex-forming ability of oligonucleotides modified with N-tert-butylguanidine- or N-tert-butyl-N'- methylguanidine-bridged nucleic acids.

Antisense oligonucleotides (ASOs) are becoming a promising class of drugs for treating various diseases. Over the past few decades, many modified nucleic acids have been developed for application to ASOs, aiming to enhance their duplex-forming ability toward cognate mRNA and improve their stability against enzymatic degradations. Modulating the sugar conformation of nucleic acids by substituting an electron-withdrawing group at the 2'-position or incorporating a 2',4'-bridging structure is a common approach for enhancing duplex-forming ability. Here, we report on incorporating an N-tert-butylguanidinium group at the 2',4'-bridging structure, which greatly enhances duplex-forming ability because of its interactions with the minor groove. Our results indicated that hydrophobic substituents fitting the grooves of duplexes also have great potential to increase duplex-forming ability.

Dramatic reduction of toxicity of Poly(hexamethylene guanidine) disinfectant by charge neutralization.

The current study aimed to investigate the toxicity of positively charged polyhexamethylene guanidine (PHMG) polymer and its complexation with different anionic natural polymers such as k-carrageenan (kCG), chondroitin sulfate (CS), sodium alginate (Alg.Na), polystyrene sulfonate sodium (PSS.Na) and hydrolyzed pectin (HP). The physicochemical properties of the synthesized PHMG and its combination with anionic polyelectrolyte complexes (PECs) namely PHMG:PECs were characterized using zeta potential, XPS, FTIR, and TG analysis. Furthermore, cytotoxic behavior of the PHMG and PHMG:PECs, respectively, were evaluated using human liver cancer cell line (HepG2). The study results revealed that the PHMG alone had slightly higher cytotoxicity to the HepG2 cells than the prepared polyelectrolyte complexes such as PHMG:PECs. The PHMG:PECs showed a significant reduction of cytotoxicity to the HepG2 cells than the pristine PHMG alone. A reduction of PHMG toxicity was observed may be due to the facile formation of complexation between the positively charged PHMG and negatively charged anionic natural polymers such as kCG, CS, Alg. Na, PSS.Na and HP, respectively, via charge balance or neutralization. The experimental results indicate that the suggested method might significantly lower PHMG toxicity while improving biocompatibility.

Synthetic and natural guanidine derivatives as antitumor and antimicrobial agents: A review.

Guanidines are fascinating small nitrogen-rich organic compounds, which have been frequently associated with a wide range of biological activities. This is mainly due to their interesting chemical features. For these reasons, for the past decades, researchers have been synthesizing and evaluating guanidine derivatives. In fact, there are currently on the market several guanidine-bearing drugs. Given the broad panoply of pharmacological activities displayed by guanidine compounds, in this review, we chose to focus on antitumor, antibacterial, antiviral, antifungal, and antiprotozoal activities presented by several natural and synthetic guanidine derivatives, which are undergoing preclinical and clinical studies from January 2010 to January 2023. Moreover, we also present guanidine-containing drugs currently in the market for the treatment of cancer and several infectious diseases. In the preclinical and clinical setting, most of the synthesized and natural guanidine derivatives are being evaluated as antitumor and antibacterial agents. Even though DNA is the most known target of this type of compounds, their cytotoxicity also involves several other different mechanisms, such as interference with bacterial cell membranes, reactive oxygen species (ROS) formation, mitochondrial-mediated apoptosis, mediated-Rac1 inhibition, among others. As for the compounds already used as pharmacological drugs, their main application is in the treatment of different types of cancer, such as breast, lung, prostate, and leukemia. Guanidine-containing drugs are also being used for the treatment of bacterial, antiprotozoal, antiviral infections and, recently, have been proposed for the treatment of COVID-19. To conclude, the guanidine group is a privileged scaffold in drug design. Its remarkable cytotoxic activities, especially in the field of oncology, still make it suitable for a deeper investigation to afford more efficient and target-specific drugs.