Imtiaj Hasan

Functional divergence among lectins can arise even in the absence of variation in carbohydrate recognition domains (CRDs), yet the underlying mechanisms remain poorly understood. Here, we investigated the structure–function relationships of hRTLs, a family of six prototype galectins from the sponge Chondrilla australiensis. Recombinant hRTLs lacking the predicted 23-amino-acid non-canonical signal peptide were expressed in Escherichia coli and analyzed for glycan-binding specificity using glycan arrays. Four members (hRTL-1, 2, 5, and 6) exhibited glycan-binding activity, whereas hRTL-3 and 4 showed markedly weaker activity. hRTL-1 and 2 displayed similar binding profiles, including recognition of TF-related glycans, while hRTL-5 preferentially bound type-1 LacNAc and hRTL-6 recognized blood group-related glycans. Structural analyses revealed distinct oligomeric states, with dimeric and tetrameric species supported by native mass spectrometry and size-exclusion chromatography, while additional higher-molecular-weight (HMW) species were observed by non-heated SDS–PAGE. Far-UV CD spectroscopy further showed that representative active and low-activity hRTLs retained β-sheet-rich secondary structures. Notably, thermal stability assays showed that multimer-forming hRTLs retained hemagglutination activity after prolonged incubation at 60 °C, whereas non-multimerizing members exhibited reduced stability. These findings show that distinct oligomeric organizations are associated with functional diversification among structurally conserved galectin CRDs and suggest that modulation of multimerization may have contributed to the evolution of early metazoan lectins.

Piper chaba , a traditionally important spice and medicinal plant, was investigated for its anticancer and antimicrobial potential using crude root extracts and root‐derived synthesized silver/silver chloride nanoparticles. Cytotoxicity assessment using the brine shrimp nauplii assay revealed LC ₅₀ values of 2445.56, 1983.56, and 1306.98 μg/mL for the aqueous PcRE (Aq), ethanolic PcRE (Et) extracts, and nanoparticle formulations PcRE (Np), respectively, indicating enhanced bioactivity of the nanoparticles. Antibacterial evaluation showed that PcRE (Np) exhibited lower MBC/MIC ratios (1.60–2.64) compared to PcRE (Aq) (2.00–2.13) and PcRE (Et) (2.17–2.20), suggesting superior bactericidal efficacy. At 250 μg/mL, PcRE (Np) demonstrated the highest antibiofilm activity against Escherichia coli (ATCC 27853) (74%), followed by PcRE (Aq) (67%) and PcRE (Et) (42%). In vivo anticancer studies using Swiss albino mice bearing Ehrlich ascites carcinoma (EAC) showed tumor growth inhibition of 26.3%, 32.0%, and 41.5% for PcRE (Aq), PcRE (Et), and PcRE (Np), respectively, at a dose of 2.5 mg/kg/day. Consistently, MTT assays against EAC cells indicated higher growth inhibition by PcRE (Np) (12.7%) compared with PcRE (Et) (7.5%) and PcRE (Aq) (6.65%) at 300 μg/mL. Treatment with PcRE (Np) significantly prolonged survival and improved hematological parameters, while also modulating cancer‐associated blood glucose levels. Histopathological analysis revealed notable hepatic tissue recovery in PcRE (Np)‐treated groups, exceeding that observed with fluorouracil. Molecular docking studies further supported these findings, demonstrating strong interactions of major P. chaba phytochemicals with COX‐2 and p53 proteins. Collectively, these results highlight PcRE (Np) as a promising antimicrobial and anticancer candidate.

Pyrimidine nucleoside derivatives have attracted considerable attention because of their broad therapeutic potential. In this study, a novel and efficient synthetic route was developed for accessing thymidine‐based nucleoside derivatives, affording high yields and confirming their structures through physicochemical, elemental, and spectroscopic analyses. The antimicrobial and antibiofilm activities of the synthesized compounds were evaluated against four bacterial strains and two fungal strains. Both the experimental and PASS‐predicted results revealed stronger antifungal activity than antibacterial activity, with remarkable potency against Aspergillus niger and Candida albicans . Notably, Compound 6 presented the lowest MIC value (e.g., 8 μg/mL) against C. albicans , which was comparable to or better than that of the standard antifungal drug fluconazole (MIC = 16 μg/mL). In addition, Compound 6 demonstrated strong antibiofilm inhibition, indicating its potential as an alternative biofilm‐targeting agent. Structure–activity relationship analysis suggested that derivatives containing long acyl chains [CH ₃ (CH ₂ ) ₇ CO–], [CH ₃ (CH ₂ ) ₈ CO–], and [CH ₃ (CH ₂ ) ₁₄ CO–] enhanced antimicrobial efficacy. Computational studies (MEP, CDFT, and molecular docking) revealed that Compound 1 was the most stable and that Compound 7 was the most chemically reactive, while docking of the R‐7 isomer with human serum albumin and DNA suggested potential anticancer effects. The dynamic stability of the docked complexes was confirmed through MM‐PBSA and molecular dynamics analyses. ADMET profiling indicated favorable pharmacokinetic properties. Overall, these thymidine derivatives display potent antimicrobial, antifungal, and antibiofilm activities, as supported by strong in silico validation, and hold promise as next‐generation antimicrobial agents.

The structure of a lectin, OXYL, derived from the feather star, Anneissia japonica (phylum Echinodermata), was analyzed from biochemistry, informatics, and 3D structural prediction. OXYL’s primary structure resembled the globular domain of complement C1q in vertebrates. Structural simulations identified OXYL as part of the C1q/TNF superfamily, characterized by a jellyroll β-sandwich fold. The subunits can form monomer to nonamer (9-mer), with trimers being the most stable. However, gel permeation chromatography indicated tetramers as the significant form. In hemagglutination inhibition tests, OXYL bound type-2 N-acetyllactosamine (LacNAc: Galβ1-4GlcNAc) and inhibited agglutination but did not bind lactose (Lac: Galβ1-4Glc). Glycan microarray analysis with 20 immobilized glycans confirmed OXYL’s specificity for type-2 LacNAc and its sialic acid α2-3 linkage. The structural simulation showed a suitable molecular docking between type-2 LacNAc and the lectin rather than lactose. OXYL bound to the LacNAc glycan on the microarray was also elucidated to capture human IgG. This finding suggests that the invertebrate C1q/TNF family lectin will mimic vertebrate C1qs, despite lacking evolutionally antibody systems, possess the potential to interact with antibodies.

Geodoram densiflorum or pink nodding orchid grows in wet habitats in Bangladesh. Rural people traditionally use this orchid’s pseudobulbs to treat skin inflammation, tumors and carbuncles. Though a protein from these bulbs previously showed antitumor activity against Ehrlich ascites carcinoma (EAC) cells in vitro, this study focused on proving this effect in vivo in a mice model and against a human cancer cell line. GDL exhibited around 45% growth inhibition against A549 cells at a concentration of 64 µg/mL implicating a caspase-dependent pathway modulated by caspase-3, -8, and -9 inhibitors. The condensed nuclei and morphological changes of GDL-treated cells indicating apoptosis also became evident by Hoechst 33342 and FITC-annexin V/PI staining. GDL up-regulated CASP9 and p53 while down-regulating PARP, MAPK, and STAT3 gene expression, suggesting the involvement of death receptor and intrinsic mitochondrial pathways. Flow cytometry analysis revealed GDL-induced G₀/G₁ phase cell cycle arrest. In vivo, GDL inhibited EAC cell proliferation by 48%, extending EAC-bearing mice lifespan by 37.05%, and improved hematological parameters, notably increasing red blood cell counts and hemoglobin levels to 2.41 × 10⁹ RBC/mL and 10.27 g/dL, respectively. These findings underscore the therapeutic potential of GDL, setting the stage for further in-depth research.

Lectins are glycan‐binding proteins that have been extensively studied for their diverse biological functions, including potential therapeutic applications. This study aimed to purify and characterize chitin‐binding lectins from two Solanaceae plants, Solanum tuberosum and Solanum annuum , and evaluate their in vivo antitumor activities against Ehrlich ascites carcinoma (EAC) cells in Swiss albino mice. The lectins, designated as Solanum tuberosum lectin (STL) and Solanum annuum lectin (SAL), were purified using affinity chromatography on an acetylated chitin column. Their molecular weights ranged from 12 to 66 kDa. Both lectins exhibited hemagglutination activity and demonstrated stability across a range of temperatures and pH levels. Carbohydrate‐binding specificity assays showed that STLs had a preference for glucose and N‐acetyl‐D‐glucosamine, while SALs bound specifically to mannose, glucose, and methyl‐α‐D‐galactopyranoside. STLs were found to be metal‐dependent, in contrast to the metal‐independent nature of SALs. Toxicity was assessed using the brine shrimp lethality assay, revealing moderate toxicity levels, with LC ₅₀ values of 154.36 μg/mL for STLs and 380.45 μg/mL for SALs. In vivo antitumor activity was determined through intraperitoneal administration of lectins to EAC‐bearing mice. STLs inhibited tumor growth by 57.85% and 73.57% at doses of 2 and 4 mg/kg/day, respectively, whereas SALs achieved tumor inhibition rates of 32.86% and 58.57% at the same doses. These antitumor effects were supported by favorable changes in hematological parameters in lectin‐treated mice. The results indicate that chitin‐binding lectins from Solanum tuberosum and Solanum annuum possess promising anticancer properties, with STLs exhibiting comparatively higher efficacy. The inhibition of EAC cell growth was attributed to apoptosis induction, as evidenced by morphological changes, upregulation of Bax and PARP, and the downregulation of Bcl‐2 expression. Further research is warranted to elucidate their molecular mechanisms of action and evaluate their potential as novel therapeutic agents in cancer treatment.