Lectins are proteins or glycoproteins of non-immune origin with carbohydrate-binding properties. They are found both prokaryotic and eukaryotic organisms. The most abundant source of the lectins are plants. Many lectins have anticancer effects by directly exerting cytotoxic effects on malignant cells or indirectly activating the immune system. Lectins also have antiviral activities. These proteins can recognise glycoproteins on the surface of enveloped viruses and bind to them. This creates a physical barrier between them and the corresponding receptors on the surface of the host cell, which prevents the virus from entering the cell and can thus effectively inhibit the replication of the virus. In this review, we focus on the anticancer activities of selected lectins and the underlying mechanisms. We also discuss different types of lectins with antiviral activity. We have paid special attention to lectins with inhibitory activity against SARS-CoV-2. Finally, we outline the challenges of using lectins in therapy and suggest future research directions.

BACKGROUND: Antiproliferative and apoptotic activities have been attributed to the phytosteroid diosgenin ((25R)-spirost-5-en-3β-ol; 1). It is known that combining glucose with two rhamnoses (the chacotrioside framework) linked to diosgenin increases its apoptotic activity. However, the effects of diosgenin glucosamine glycosides on different cancer cell types and cell death have not been entirely explored.
RESULTS: This study reports the antiproliferative, cytotoxic, and apoptotic activities of diosgenin and its glycosylated derivative ((25R)-spirost-5-en-3β-yl β-D-glucopyranoside; 2). It also explores the effects of two diosgenin glucosamine derivates, diosgenin 2-acetamido-2-deoxy-β-D-glucopyranoside (3), and diosgenin 2-amino-2-deoxy-β-D-glucopyranoside hydrochloride (4), on different cancer cell lines. We found that all the compounds affected proliferative activity with minimal toxicity. In addition, all cancer cell lines showed morphological and biochemical characteristics corresponding to an apoptotic process. Apoptotic cell death was higher in all cell lines treated with compounds 2, 3 and 4 than in those treated with diosgenin. Moreover, compounds 3 and 4 induced apoptosis better than compounds 1 and 2. These results suggest that combining glucosamine with modified glucosamine attached to diosgenin has a greater apoptotic effect than diosgenin or its glycosylated derivative (compound 2). Furthermore, diosgenin and the abovementioned glycosides had a selective effect on tumour cells since the proliferative capacity of human lymphocytes, keratinocytes (HaCaT) and epithelial cells (CCD841) was not significantly affected.
CONCLUSIONS: Altogether, these results demonstrate that diosgenin glucosamine compounds exert an antiproliferative effect on cancer cell lines and induce apoptotic effects more efficiently than diosgenin alone without affecting non-tumour cells.
CONCLUSIONS: This study evidences the pro-apoptotic and selective activities of diosgenyl glucosamine compounds in cancer cell lines.

Clinical treatment with the antineoplastic drug irinotecan (IRI) is often hindered by side effects that significantly reduce the quality of life of treated patients. Due to the growing public support for products with Δ9-tetrahydrocannabinol (THC), even though relevant scientific literature does not provide clear evidence of their high antitumour potential, some cancer patients take unregistered preparations containing up to 80 % THC. This study was conducted on a syngeneic colorectal cancer mouse model to test the efficiency and safety of concomitant treatment with IRI and THC. Male BALB/c mice subcutaneously injected with CT26 cells were receiving 60 mg/kg of IRI intraperitoneally on day 1 and 5 of treatment and/or 7 mg/kg of THC by gavage a day for 7 days. Treatment responses were evaluated based on changes in body, brain, and liver weight, tumour growth, blood cholinesterase activity, and oxidative stress parameters. Irinotecan\'s systemic toxicity was evidenced by weight loss and high oxidative stress. The important finding of this study is that combining THC with IRI diminishes IRI efficiency in inhibiting tumour growth. However, further studies, focused on more subtle molecular methods in tumour tissue and analytical analysis of IRI and THC distribution in tumour-bearing mice, are needed to prove our observations.
Kliničko liječenje antineoplastičnim lijekom irinotekanom (IRI) često je otežano nuspojavama koje značajno smanjuju kvalitetu života liječenih bolesnika. Zbog sve veće javne potpore proizvodima s Δ9-tetrahidrokanabinolom (THC), iako relevantna znanstvena literatura ne daje jasne dokaze o njihovu visokom antitumorskom potencijalu, oboljeli od raka uzimaju neregistrirane pripravke koji sadržavaju i do 80 % THC-a. Ova studija provedena je na modelu singeničnoga tumora debelog crijeva u miševa kako bi se testirala učinkovitost i sigurnost istodobnog tretmana irinotekanom i THC-om. Mužjaci BALB/c miševa kojima su supkutano injicirane CT26 stanice primili su 60 mg/kg IRI-ja intraperitonealno prvi i peti dan i/ili 7 mg/kg THC-a oralno svaki dan tijekom sedam dana. Učinkovitost tretmana procijenjena je na temelju promjena u težini tijela, mozga i jetre, rasta tumora, aktivnosti kolinesteraza u krvi i parametara oksidacijskoga stresa. Sistemska toksičnost irinotekana potvrđena je smanjenjem težine miševa i povećanjem parametara oksidacijskoga stresa. Značaj je rezultata ove studije u smanjenoj učinkovitosti IRI-ja u inhibiciji rasta tumora tijekom istodobnog uzimanja s THC-om. Međutim, potrebna su daljnja istraživanja usmjerena na suptilnije molekularne metode u tumorskom tkivu i analitička analiza distribucije IRI-ja i THC-a u miševa s tumorom kako bi se dokazala naša opažanja.

Proteolysis-targeting chimaera (PROTAC) has received extensive attention in industry. However, there are still some limitations that hinder its further development. In a previous study, our group first demonstrated that the HSP90 degrader BP3 synthesised by the principle of PROTACs showed therapeutic potential for cancer. However, its application was hindered by its high molecular weight and water insolubility. Herein, we aimed to improve these properties of HSP90-PROTAC BP3 by encapsulating it into human serum albumin nanoparticles (BP3@HSA NPs). The results demonstrated that BP3@HSA NPs showed a uniform spherical shape with a size of 141.01 ± 1.07 nm and polydispersity index < 0.2; moreover, BP3@HSA NPs were more readily taken up by breast cancer cells and had a stronger inhibitory effect in vitro than free BP3. BP3@HSA NPs also demonstrated the ability to degrade HSP90. Mechanistically, the improved inhibitory effect of BP3@HSA NPs on breast cancer cells was related to its stronger ability to induce cell cycle arrest and apoptosis. Furthermore, BP3@HSA NPs improved PK properties and showed stronger tumour suppression in mice. Taken together, this study demonstrated that hydrophobic HSP90-PROTAC BP3 nanoparticles encapsulated by human serum albumin could improve the safety and antitumour efficacy of BP3.

The colchicine binding site of tubulin is a promising target for discovering novel antitumour agents. Previously, we identified 2-aryl-4-amide-quinoline derivatives displayed moderate tubulin polymerisation inhibitory activity and broad-spectrum in vitro antitumour activity. In this study, structure based rational design and systematic structural optimisation were performed to obtain analogues C1∼J2 bearing diverse substituents and scaffolds. Among them, analogue G13 bearing a hydroxymethyl group displayed good tubulin polymerisation inhibitory activity (IC50  =  13.5 μM) and potent antiproliferative activity (IC50 values: 0.65 μM∼0.90 μM). G13 potently inhibited the migration and invasion of MDA-MB-231 cells, and displayed potent antiangiogenic activity. It efficiently increased intracellular ROS level and decreased MMP in cancer cells, and obviously induced the fragmentation and disassembly of the microtubules network. More importantly, G13 exhibited good in vivo antitumour efficacy in MDA-MB-231 xenograft model (TGI  =  38.2%; i.p., 30 mg/kg).

Mutation of FLT3 protein kinase is often associated with deregulated cell proliferation in acute myeloid leukemia and the inhibition of this kinase is a potential therapeutic strategy. We report a novel series of 3,5,7-trisubstituted pyrazolo[1,5-a]pyrimidines prepared in an effort to study their biological activity particularly toward FLT3-ITD and its downstream regulators as well as toward CDK2 and CDK9. Derivative 10b was capable to strongly inhibit all kinases and its selectivity in FLT3-ITD expressing cell lines MOLM13 and MV4-11 was in line with FLT3-ITD inhibition. Further biochemical analyses and molecular docking confirmed FLT3 as a cellular target of 10b.

BACKGROUND: Cluster of differentiation (CD) 73-targeted immunotherapy and CD73 inhibition may reduce adenosine production, which can augment the host and/or immunotherapy response to tumours. We aimed to assess the safety and tolerability, pharmacokinetics, and antitumour activity of oleclumab, an anti-CD73 monoclonal antibody, in adult Japanese patients with advanced solid malignancies resistant to standard therapy.
METHODS: In this phase I, single-centre, open-label study, patients received oleclumab 1500 mg (Cohort 1) or 3000 mg (Cohort 2) intravenously every 2 weeks.
RESULTS: In total, six patients were enrolled in the study (three in each cohort), and all six patients received the study treatment. The median patient age was 56.0 years and 4/6 were males. All patients (100%) reported adverse events (AEs) during the study; five (83.3%) patients reported AEs related to the study treatment. One (16.7%) patient reported a Grade 3 AE (neutrophil count decreased) that was not related to the study treatment. No AEs with an outcome of death were reported, and no patients reported AEs or serious AEs leading to oleclumab discontinuation/dose interruption. No dose-limiting toxicities were reported, and no patient discontinued due to an AE related to the study treatment. Oleclumab exposure increased dose proportionally. No patient achieved disease control at 8 weeks, and all six patients developed progressive disease.
CONCLUSIONS: Oleclumab was well tolerated in adult Japanese patients with advanced solid malignancies and no unexpected safety concerns were raised; oleclumab exposure increased with dose. Future studies on combination therapy with other agents are warranted.

Although it is known that the first case of cancer was recorded in ancient Egypt around 1600 BC, it was not until 1917 during the First World War and the development of mustard gas that chemotherapy against cancer became relevant; however, its properties were not recognised until 1946 to later be used in patients. In this sense, the use of metallopharmaceuticals in cancer therapy was extensively explored until the 1960s with the discovery of cisplatin and its anticancer activity. From that date to the present, the search for more effective, more selective metallodrugs with fewer side effects has been an area of continuous exploration. Efforts have led to considering a wide variety of metals from the periodic table, mainly from the d-block, as well as a wide variety of organic ligands, preferably with proven biological activity. In this sense, various research groups have found an ideal binder in Schiff bases, since their raw materials are easily accessible, their synthesis conditions are friendly and their denticity can be manipulated. Therefore, in this review, we have explored the anticancer and antitumor activity reported in the literature for coordination complexes of d-block metals coordinated with tridentate Schiff bases (O N O and O N N) derived from salicylaldehyde. For this work, we have used the main scientific databases CCDC® and SciFinder®.

A promising hydrazide based small molecule lead as a potent and selective histone deacetylase 3 (HDAC3) inhibitor has been developed from a small series of synthesized novel chemical entities. The lead compound (4e) displayed high HDAC3 inhibitory potency (IC50 = 15.41 nM) and a minimum of 18-fold selectivity over other HDAC isoforms. It also exhibited potent cytotoxicity against several cancer cell lines with minimal toxicity against normal cell lines tested. Compound 4e also enhanced acetylation levels on H3K9, H4K12 and H3K27 both in vitro and in vivo. It also induced cell cycle arrest at the G2/M phase in B16F10 and 4T1 cells. It caused significant apoptosis and upregulated the expression of caspase-3, caspase-7, cytochrome c and downregulated the expression of BCL2 in tumour tissue. In addition, the downregulation of CD44, EGFR and Ki-67 suggested the potential of compound 4e in reducing cell proliferation and metastasis in mice. Further, a marked decrease in the tumour volume was observed with no general toxicity in the major organs when treated with 4e in the 4T1-Luc xenograft mouse model. Therefore, compound 4e is a promising candidate selectively targeting HDAC3 with a significant antitumour activity that can be evaluated further in preclinical and clinical evaluation.

Based on the previous synthesis of tetracyclic and tricyclic benzimidazoles starting from 1,4:3,6-dianhydro-d-fructose and o-phenylenediamines, a series of 5(6)-amino substituted tetracyclic and tricyclic benzimidazolequinones were obtained through the oxidation of 4,7-dimethoxy-benzimidazole analogues with bis(trifluoroacetoxy)iodobenzene (PIFA) and subsequent substitution with various aliphatic and aromatic amines. Biological evaluations of the target benzimidazolequinones indicated that all the arylamino-substituted benzimidazolequinones possess potent antitumour activity against human gastric cancer cells (MGC-803), especially compound a21-2. Furthermore, compound a21-2 inhibits gastric cancer cells proliferation and cell colony formation. Mechanistic investigations showed that compound a21-2 induces ROS production, which subsequently causes DNA damage and activation of ATM/Chk2, leading to G2/M phase arrest. ROS activates the c-Jun N-terminal kinase (JNK) pathway to induce mitochondrial-mediated apoptosis. In vivo studies showed that compound a21-2 inhibits the growth of tumours in nude mice without significant systemic toxicity. These findings suggest that compound a21-2 represents a promising candidate antitumour drug.