Search Results (3,877)

The genus Tamarix L. includes several species widely used in traditional medicine for their therapeutic properties. This study aims to evaluate the bioactive potential of Tamarix gallica extracts from Western Algeria using an integrated in vitro and in silico approach. GC–MS analysis with BSTFA derivatization was performed to characterize the chemical profile of the methanolic fraction. In addition, total phenolic, flavonoid, and tannin contents were determined in methanolic extracts of leaves and stems. The biological activities were assessed using antioxidant (DPPH, ABTS, β-carotene, FRAP, O-phenanthroline, and cupric reducing assays), antimicrobial, antidiabetic, and anti-Alzheimer in vitro assays. Molecular docking was conducted to evaluate the inhibitory potential of selected flavonoids against α-amylase, acetylcholinesterase, and butyrylcholinesterase. Results revealed a rich metabolite profile dominated by long-chain aliphatic alcohols (including hentriacontan-12-ol), phytosterols (β-sitosterol), fatty acids, phenolic derivatives, and sugar alcohols. The extracts exhibited strong antioxidant activity (IC₅₀ = 1.34 ± 0.43 and 12.32 ± 0.36 μg·mL⁻¹), significant antimicrobial effects against the tested pathogens, and notable antidiabetic and anticholinesterase activities (IC₅₀ = 78.65 ± 1.43 and 98.37 ± 1.07 μg·mL⁻¹). Molecular docking analysis supported these findings, showing strong binding affinities of quercetin and rhamnetin toward the target enzymes. Overall, T. gallica exhibits promising multifunctional bioactivities with potential pharmaceutical relevance. Full article

Background: Type 2 diabetes mellitus (T2DM) is a global health challenge characterized by chronic hyperglycemia and oxidative stress. Pithecellobium dulce root has long been recognized for its antidiabetic potential; however, its specific bioactive constituents and mechanisms of action remain poorly defined. This study aimed to evaluate the antidiabetic and antioxidant properties of extracts and isolated molecules from P. dulce root bark. Methods: The DCM/MeOH crude extract of P. dulce root bark was fractionated with n-hexane (PDEH) and ethyl acetate (PDAE), followed by chromatographic purification and spectroscopic characterization, yielding seventeen compounds (1–17). The antioxidant activity (DPPH, ABTS, FRAP) and antidiabetic potential of PDEH, PDAE, and 1–17 were assessed in vitro using yeast-derived enzymes and in silico (targeting human α-glucosidase [PDB: 2QLY] and human α-amylase [PDB: 4GQR]). The in vitro α-glucosidase experiments used saccharomyces cerevisiae enzyme, which varies from the human target. Therefore, these results should be taken as preliminary screening data that needs confirmation with human enzymes. Results: Compound 1 was identified as new, while 2 was isolated for the first time from a natural source. The cell-free chemical tests DPPH, ABTS, and FRAP measured antioxidant capability. These tests quantify radical-scavenging and electron-transfer capabilities in vitro and are preliminary chemical screening methods. They do not directly represent biological antioxidant activity in cells or organisms. PDEH demonstrated strong radical scavenging against DPPH (IC₅₀ = 15.30 μg/mL) and ABTS (IC₅₀ = 12.80 μg/mL), while pristriol (16) showed ferric reducing power (EC₅₀ = 4200 μM FeSO₄/g). Enzyme inhibition assays demonstrated activity against α-amylase (IC₅₀ 53.88–112.24 µg/mL; acarbose IC₅₀ = 91.20 µg/mL) and α-glucosidase (IC₅₀ 18.38–136.88 µg/mL; acarbose IC₅₀ = 11.31 µg/mL). Compounds 15, 1, and 2 showed superior activity compared to acarbose for α-amylase, with effect sizes (Cohen’s d) of 2.15, 0.94, and 0.82, respectively, and IC₅₀ values of 53.88, 88.15, and 92.62 µg/mL; for α-glucosidase, IC₅₀ values were 18.38, 39.25, and 36.40 µg/mL, respectively. Docking studies supported these findings, revealing binding energies of −9.08, −8.34, and −7.22 kcal/mol for compounds 1, 2, and 15 with α-amylase, and −10.35 and −9.79 kcal/mol for compounds 1 and 2 with α-glucosidase. ADME profiling further identified 1 and 2 as promising lead candidates for dual-enzyme inhibition. Conclusions: P. dulce root bark represents a potent source of bioactive molecules with both antioxidant and dual-enzyme-inhibitory properties. These findings validate its traditional use and highlight its potential in the development of multitarget therapies for T2DM management. Full article

Skin aging is associated with oxidative stress, extracellular matrix degradation, and dysregulation of melanogenesis, leading to wrinkles, loss of elasticity, and hyperpigmentation. Natural plant-derived compounds have attracted increasing interest as multifunctional cosmetic ingredients due to their antioxidant and anti-aging properties. Mai-Kae-Den-Klong (MKDK), a traditional Thai longevity herbal formula composed of Albizia procera (Roxb.) Benth., Cyperus rotundus L., Diospyros rhodocalyx Kurz, Piper nigrum L., Streblus asper Lour., and Tinospora crispa (L.) Hook.f. & Thomson, has historically been used to promote vitality and healthy aging; however, its potential application as a cosmetic anti-aging ingredient remains scientifically unexplored. Therefore, this study investigated the anti-aging potential of MKDK extract using integrated enzyme-based bioassays and in silico approaches. Phytochemical profiling of the ethanolic extract was performed using LC-MS analysis, revealing diverse bioactive constituents, including flavonoids, phenolic glycosides, alkaloids, and terpenoids, with (−)-epicatechin, procyanidin B1, and piperine identified as major metabolites. Antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays, while inhibitory activities against tyrosinase, collagenase, elastase, and hyaluronidase were assessed to determine skin anti-aging potential. The extract exhibited strong antioxidant activity, with IC₅₀ values of 17.23 ± 2.11 µg/mL for DPPH and 11.87 ± 1.77 µg/mL for ABTS assays. In addition, the extract demonstrated inhibitory effects against tyrosinase (IC₅₀ = 41.25 ± 1.56 µg/mL), elastase (IC₅₀ = 49.51 ± 3.69 µg/mL), collagenase (IC₅₀ = 61.54 ± 2.88 µg/mL), and hyaluronidase (IC₅₀ = 63.74 ± 6.32 µg/mL), suggesting multifunctional anti-aging properties associated with skin brightening and extracellular matrix preservation. Network pharmacology analysis predicted multiple aging-related signaling pathways, particularly the FoxO signaling pathway, which is associated with oxidative stress regulation and longevity. Molecular docking analysis further demonstrated favorable binding affinities of procyanidin B1, epicatechin, and piperine toward skin-aging-related enzymes, supporting their potential contribution to the observed bioactivities. Overall, these findings suggest that MKDK possesses promising cosmeceutical potential as a natural multifunctional anti-aging ingredient and provides scientific support for the application of traditional Thai herbal formulations in cosmetic and skin health products. Full article

Compounds from olive (Olea europaea L.) and pomegranate (Punica granatum L.) have many beneficial effects on human health. This review paper considers the inhibitory potential, under in vitro conditions, of bioactive components of olive and pomegranate on different enzyme systems. Research shows that olive polyphenols (oleuropein, hydroxytyrosol, luteolin, and oleocanthal), as well as pomegranate polyphenols (punicalagin, urolithin A, ellagic acid), inhibit cyclooxygenase and lipoxygenase enzymes, which are associated with inflammatory processes. They also show an inhibitory effect on acetylcholinesterase, butyrylcholinesterase, and β-secretase, which opens up the possibility of a strong neuroprotective effect. Olive and pomegranate polyphenols also have an inhibitory effect on enzymes involved in carbohydrate metabolism, such as amylase and glucosidase, and can help fight diabetes and regulate human metabolism. In addition, polyphenols and extracts of both plants showed an inhibitory effect on cytochrome P450 enzymes, which metabolize most drugs. These data open up the possibility of interactions with certain groups of drugs. The current evidence supports the view that olive and pomegranate polyphenols act as biologically versatile compounds with considerable pharmaceutical and nutraceutical potential. Future investigations integrating enzymology, metabolomics, molecular docking, and clinical validation will be essential for translating these promising in vitro findings into evidence-based therapeutic applications. Full article

Background: Reverse transcription is a key step in emerging RNA diagnostics, but reverse transcriptase (RT) enzymes often fail in the presence of inhibitors carried over from clinical samples or introduced during RNA extraction. Here, we dissect the molecular basis of inhibitor resistance in five engineered variants (V1 to V5) of Moloney Murine Leukemia Virus RT, originally optimized for thermostability and catalytic activity. Methods: Using a systematic framework that integrates structural analysis, thermal profiling, and diagnostic benchmarking, we evaluated cDNA synthesis from 40 to 70 °C under a panel of 11 clinically relevant inhibitors. Results: Across 30 mutations assessed, a recurrent set of substitutions (E69K, E302K/R, W313F, and N454K), present in RT V1 and V4, was associated with enhanced robustness, consistent with strengthened enzyme–nucleic acid engagement, while L435G likely contributes by modulating conformational flexibility. Notably, inhibitor tolerance was maximal at moderate reaction temperatures (≈40 °C), where productive enzyme–substrate interactions best offset inhibitory stress, while the wild-type enzyme was effectively inactivated by several inhibitors under the conditions tested. Although the engineered RTs remained catalytically competent at higher temperatures, increased thermal stress may destabilize productive enzyme–nucleic acid complexes, reducing resistance under inhibitory conditions. Conclusions: Together, these findings support substrate engagement as an important determinant of RT robustness and provide practical guidance for engineering inhibitor-resistant RTs for high-sensitivity RT-qPCR. Full article

Hypertension is one major risk factor of cardiovascular diseases, and RAS plays vital role during the development of hypertension. To obtain a novel antihypertensive peptide, Coix glutelin was hydrolyzed by trypsin and further separated by Sephadex G10. Based on 751 identified sequences, pharmacophore mapping, molecular docking, and in silico proteolysis were applied to screen and optimize the candidate sequence. Finally, a novel peptide, ENWAAL, was generated with IC₅₀ of 210.57 μM, which acted with ACE in a competitively inhibitory pattern. The in vivo antihypertensive effect was evaluated in SHRs. Significant improvements were observed in hypertension-related characteristics, including blood pressure, cardiac structure and function, and serum angiotensin II (Ang II) level. In the brain, quantitative real-time PCR analysis revealed significant downregulation of angiotensin II type 1 receptor (AT1R) mRNA expression, concomitant with upregulation of angiotensin-converting enzyme 2 (ACE2) and MAS receptor. The protein expression of ACE and AT1R in the ENWAAL group also significantly decreased. This study can provide a candidate antihypertensive drug targeting RAS. Full article

In this study, a new range of carbazole linked mono- and bis-ester derivatives were successfully synthesized and evaluated for their in vitro anti-diabetic activity through α-amylase and α-glucosidase inhibition. The synthetic approach for the preparation of mono-esters 5a–j and bis-esters 7a–j was achieved by the reaction of carbazole-3-methanol 4 and carbazole-3,6-dimethanol 6 with a variety of acyl chlorides. The targeted compounds displayed generally weak α-amylase inhibition but significant and selective inhibition against α-glucosidase. Among them, 7a, 7g, and 7j exhibited dual inhibitory activity, while 7f was selective for α-glucosidase, and 7d and 5g for α-amylase. Notably, 7g was the most potent compound (IC₅₀ = 22.79 µM), surpassing Acarbose. In addition, molecular docking studies of the synthesized compounds were carried out to investigate their interactions with the α-glucosidase enzyme. Overall, targeted carbazole-based ester derivatives show promising results as selective anti-diabetic agents. Full article

Luteolin and its derivative glycosides (cynaroside, orientin and isoorientin) are compounds with a flavonoid structure of plant origin. There are different studies in the literature on the antioxidant capacities of the structures and their inhibition effects on some enzymes. In this study, the antioxidant capacities of each structure were determined comparatively, and their inhibitory effects against enzymes associated with different diseases such as acetylcholinesterase, butyrylcholinesterase, α-glycosidase and α-amylase were evaluated by comparative investigation in vitro and in silico. Antioxidant capacities were determined for each structure by iron ions (Fe³⁺), cupric ions (Cu²⁺), Fe³⁺−Triphenyltetrazolium chloride (TPTZ) reduction methods and 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), N,N-dimethyl-p-phenylenediamine (DMPD) radical scavenging methods. According to the results obtained, it was determined that the antioxidant capacities of the structures were close to or better than butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), trolox, α tocopherol and ascorbic acid, which are used as standard antioxidants. The results of the study, which was conducted to determine the inhibition effects of the structures on the determined enzymes, were found to coincide experimentally and theoretically. According to the inhibition results, the best inhibitors were found as orientin (IC₅₀: 27.729 nM) for the human carbonic anhydrase I (hCA I), cynaroside (IC₅₀: 18.24 nM) for the human carbonic anhydrase I (hCA II), isoorientin (IC₅₀: 1.93 nM) for the acetylcholinesterase (AChE), and cynaroside (IC₅₀: 6.41 and 7.15 nM) for the butyrylcholinesterase (BChE) and α-glycosidase enzymes. Additionally, absorption, distribution, metabolism, and excretion (ADME) profiles and toxicity assessments of the structures were determined in a virtual environment. Full article

Plants of the genus Astragalus are recognized as rich sources of bioactive compounds with antioxidant and therapeutic potential; however, European species remain less explored than the well-known Astragalus membranaceus (Fisch.) Bunge. The aim of this study was to compare the phytochemical composition and in vitro biological activity of selected Astragalus species occurring in Poland (A. cicer L., A. glycyphyllos L., A. membranaceus). Phenolic compounds in methanolic extracts obtained from the roots and aerial parts were analyzed using spectrophotometric methods and UHPLC–DAD–ESI/TOF–MS. Antioxidant activity was evaluated using DPPH, ABTS, FRAP, CUPRAC, metal chelation, superoxide radical scavenging, and lipid peroxidation (TBARS) assays. Additionally, enzyme inhibition toward α-amylase, lipase, hyaluronidase, tyrosinase, and butyrylcholinesterase was assessed. The root of A. membranaceus exhibited the highest total phenolic content (199.84 ± 3.64 mg GAE/g extract) and the strongest antioxidant activity (DPPH IC₅₀ = 36.53 ± 1.22 µg/mL; ABTS IC₅₀ = 26.31 ± 0.03 µg/mL), as well as the most pronounced α-amylase inhibition (IC₅₀ = 17.78 ± 1.16 µg/mL). It also demonstrated moderate protective effects against AAPH-induced lipid peroxidation. The herb of A. cicer showed moderate radical scavenging capacity and the most effective inhibition of lipid peroxidation at higher concentrations. Extracts of A. glycyphyllos displayed weaker radical scavenging but notable metal-chelating properties. Selected extracts also exhibited moderate inhibitory activity against tyrosinase and butyrylcholinesterase. A. membranaceus remains the most potent source of phenolic compounds and antioxidant activity; European species such as A. cicer and A. glycyphyllos represent promising, locally available alternatives and may be used in phytotherapy and functional products. Full article

Plant-based symbiotic systems are often limited by poor storage stability and inconsistent biofunctional performance. This study evaluated the stability and functionality of a fermented blend based on sacha inchi (Plukenetia volubilis) oil press cake (SIC) and yacon (Smallanthus sonchifolius) flour (YF) as sources of protein and fructooligosaccharides (FOS), respectively, using two processing strategies: fermentation with Lactobacillus rhamnosus (T1) and combined enzymatic hydrolysis with Alcalase and fermentation with Lactobacillus plantarum (T2). Both treatments maintained viable cell counts (VCC) above probiotic thresholds (>10⁶ CFU mL⁻¹) during 28 days of storage at 4 °C, confirming their suitability as probiotic carriers. Notably, T2 significantly enhanced metabolic activity, as evidenced by higher organic acid production and increased soluble protein content due to Alcalase-mediated hydrolysis, which promoted the generation of bioactive peptides associated with improved antioxidant and antihypertensive activities. Biofunctional properties, including total phenolic content, antioxidant capacity (AC), and angiotensin-converting enzyme (ACE) inhibitory activity, remained stable throughout storage, while FOS degradation was minimal, confirming preservation of prebiotic functionality. LC–MS/MS Q-TOF analysis revealed a complex phenolic profile that was differentially modulated by lactic acid fermentation, with L. plantarum (T2) promoting extensive phenolic biotransformation and increased metabolite diversity, whereas L. rhamnosus (T1) largely preserved the original phenolic profile. These findings demonstrate that the synergistic interaction between enzymatic hydrolysis and L. plantarum fermentation promoted peptide release, intensified microbial metabolism, and enhanced phenolic biotransformation, thereby contributing to the superior functional properties observed in T2, while maintaining stable biofunctional characteristics throughout refrigerated storage in both treatments. Full article

This study provides a comprehensive evaluation of the chemical composition and the biological properties of Reseda alba L., commonly known as white mignonette. Extracts obtained from leaves (L), flowers (F), stems (S), and immature fruits (Fr) by ultrasound-assisted extraction (UAE) were assessed for their antioxidant, anti-inflammatory, and growth-inhibitory activity, and chemically characterized by an analytical approach based on liquid chromatography/electrospray/high-resolution tandem–mass spectrometry (LC-ESI/HRMS/MS). The resulting chromatographic profile revealed 30 major constituents belonging to the flavonoids, glucosinolates, phenolic acids, and polar lipids, as well as hydroxy fatty acid classes. Naringenin-di-C-glucoside, isorhamnetin-O-deoxyhexosyl-hexoside, kaempferol-O-dideoxyhexosyl-hexoside, and isorhamnetin O-dideoxyhexoside are reported here for the first time in the genus Reseda. The Fr extract exhibited the highest anti-inflammatory and radical scavenging properties, likely due to its higher flavonoid content compared to the other extracts. On the other hand, the F extract significantly reduced the viability of colorectal adenocarcinoma (CaCo-2) and hepatocarcinoma (HepG-2) cells. Lactate dehydrogenase (LDH) release assay showed that the treatments with R. alba did not induce the release of the marker enzyme in CaCo-2 and HepG-2 cells, suggesting the involvement of a different cell death pathway. Overall, the bioactivities observed among the different plant organs highlight the beneficial potential of R. alba and provide a rationale for future bioactivity-guided isolation studies. Full article

Passion fruit (Passiflora edulis) processing generates by-products rich in bioactive secondary metabolites; however, comparative characterization across fruit fractions remains limited. This study evaluated pulp (PPE), pulp-seed (PSC), and seed (PSE) extracts for extraction yield, metabolite composition, antioxidant and anti-aging activities, and collagen-stimulatory activity in human skin fibroblasts. Extraction yields followed the order PPE > PSE > PSC. Untargeted LC–QTOF/MS profiling revealed distinct phytochemical patterns, with piceatannol enriched in PSE and trans-ferulic acid broadly abundant across all fractions. PSE showed the strongest antioxidant activity in DPPH and FRAP assays, and both PSE and PSC inhibited collagenase and hyaluronidase, while PPE showed negligible activity. All extracts were non-cytotoxic up to 0.1 mg/mL. At this concentration, PSC enhanced type I collagen production by 8.07 ± 2.24%, significantly exceeding PSE (2.26 ± 1.33%), while piceatannol stimulated collagen synthesis by 11.34 ± 1.50%, comparable to L-ascorbic acid (13.90 ± 1.16%). Molecular docking suggested that piceatannol and trans-ferulic acid may contribute to the observed anti-aging effects by interacting favorably with collagenase and hyaluronidase. These findings demonstrate that passion fruit by-product fractions exhibit complementary bioactivity profiles, with PSE favoring antioxidant and enzyme inhibitory effects and PSC enhancing collagen biosynthesis, as natural anti-aging applications. Full article

Adolescence is a developmental stage marked by dynamic interactions between diet, the gut microbiome and endocrine maturation, creating a physiological environment in which early metabolic disturbances can rapidly translate into long-term cardiovascular vulnerability. This narrative review summarises the latest research on the diet–microbiome–hormone axis in adolescents, focusing on the metabolic pathways through which microbial metabolites influence host physiology. Short-chain fatty acids (SCFAs), microbially transformed bile acids and postbiotic signalling molecules regulate enteroendocrine communication, insulin sensitivity, vascular function and inflammatory tone, thereby linking dietary exposures to early cardiometabolic alterations. Dysbiosis, driven by ultra-processed dietary patterns, low fibre intake and reduced microbial diversity, promotes metabolic endotoxemia, neuroendocrine imbalance and endothelial impairment, all of which are recognised as early indicators of cardiovascular disease. A distinctive contribution of this review is the integration of PF into the adolescent cardiometabolic framework. This emerging biotechnological process enables the controlled production of structurally defined bioactive compounds, including angiotensin-converting enzyme (ACE) inhibitory peptides, targeted prebiotic oligosaccharides, fermentable substrates that promote SCFA formation, microbially derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), phytosterols and purified postbiotics. These compounds modulate several regulatory pathways, such as the renin–angiotensin–aldosterone system, lipid and bile acid metabolism, gut barrier stability, inflammatory signalling and endocrine axes involving glucagon-like peptide-1 (GLP-1), peptide YY (PYY), leptin, insulin sensitivity and growth hormone/insulin-like growth factor-1 (GH/IGF-1) dynamics. By situating precision fermentation within the broader context of adolescent metabolic susceptibility, this review highlights its potential to support microbiome resilience, stabilise hormonal regulation and mitigate early cardiovascular risk. However, further adolescent-specific clinical trials and long-term safety assessments are required to translate these advances into effective public health strategies. Full article

The valorization of agri-food by-products generated during juice extraction represents a key strategy within circular economy frameworks, as it reduces the environmental impact of waste disposal while creating added value and improving the food supply chain. In this work, five betaine-based natural deep eutectic solvents (NaDES) differing in their hydrogen-bond donors, namely citric acid, lactic acid, acetic acid, glycerol, and ethylene glycol, were used for the green extraction of blueberry pomace, a largely underutilized by-product that is nevertheless rich in bioactive compounds. The extracts were characterized by liquid chromatography coupled with diode-array and tandem mass spectrometric detection, allowing targeted profiling of anthocyanins and non-anthocyanin phenolics, including phenolic acids, flavonoids, and phenolic aldehydes. The extraction performance of NaDES was benchmarked against conventional solvents (water and ethanol) to evaluate differences in selectivity and efficiency toward distinct phenolic classes. Antioxidant capacity was determined using DPPH and ABTS radical scavenging assays. Among the NaDES systems, the betaine–citric acid NaDES extract exhibited notable phenolic recovery together with marked radical scavenging activity. After evaluating its inhibitory activity against elastase and tyrosinase, enzymes involved in the skin aging process, the selected NaDES extract was incorporated into a natural-based antiaging cosmetic formulation, and its main physicochemical properties were assessed to verify suitability for topical application. This study demonstrated that the use of NaDES represents an environmentally friendly and sustainable approach to transform blueberry by-products into high-value, safe, and ready-to-use cosmetic functional ingredients without the need for solvent removal. Full article

Background/Objectives: Diabetes mellitus (DM) is a critical metabolic condition with escalated blood glucose levels caused by insulin resistance, restricted insulin production, and the activity of alpha-amylase and alpha-glucosidase enzymes. Methods: This current work focuses on the synthesis and evaluation of novel Pyrimidine-derived pyrazole-based thiadiazole derivatives to target DM by inhibiting α-amylase and α-glucosidase. Results: The findings exhibited that, except for three compounds, all other synthesized derivatives inhibited α-amylase and α-glucosidase enzymes with IC₅₀ values ranging from 5.17 μM to 29.84 μM on α-amylase and 7.60 μM to 31.62 μM on α-glucosidase, in comparison to the standard drug Acarbose (α-amylase IC₅₀ = 8.25 ± 0.80 μM; α-glucosidase IC₅₀ = 10.75 ± 1.10 μM). Analogs 8g, 8k, and 8b displayed superior or comparable inhibitory activity compared to the reference drug Acarbose. The inhibition potential of the derivatives can be attributed to their stable contacts with crucial amino acid residues of targeted enzymes, as shown through molecular docking analysis. Moreover, DFT-calculated HOMO–LUMO parameters and electrostatic potential (ESP) maps were used to gain complementary insight into the electronic characteristics, charge distribution, and potential interaction behavior of the synthesized derivatives, which supported the molecular docking observations. Conclusions: Experimental outcomes and in silico support display that these derivatives serve as potential leads for anti-diabetic drug development. These potent pyrimidine-derived pyrazole-based thiadiazole derivatives were comparable to an existing diabetic mellitus inhibitor, specifying potential for further therapeutic development and optimization against diabetic mellitus. Full article