Pharmacological Profile of Thiadiazole

Abstract

Thiadiazoles are aromatic, electron-deficient five-membered heterocycles containing sulfur and nitrogen atoms, widely recognized as versatile scaffolds in medicinal and agricultural chemistry. Their conjugated and lipophilic ring system acts as an effective bioisostere for thiazole, oxadiazole, oxazole, pyrimidine, and benzene, contributing to enhanced stability and improved biological activity. A broad range of thiadiazole derivatives has demonstrated significant antimicrobial, antifungal, insecticidal, antiviral, anticancer, and antidiabetic activities. Among these, 1,3,4-thiadiazoles are particularly prominent due to their favorable physicochemical properties and diverse structural adaptability. Numerous studies report potent antimicrobial and antifungal effects, including submicromolar antimycobacterial activity and strong inhibition of clinically important pathogens. Thiadiazole-based frameworks also exhibit promising insecticidal and antiviral potential, with several derivatives outperforming standard reference agents. In oncology research, thiadiazole hybrids have shown notable cytotoxicity across multiple human cancer cell lines, with some compounds reaching nanomolar efficacy. Furthermore, thiadiazole derivatives display remarkable antidiabetic activity through ?-amylase and ?-glucosidase inhibition, with several compounds demonstrating superior potency to acarbose. Overall, thiadiazole heterocycles continue to serve as valuable lead structures for the development of multifunctional therapeutic and agrochemical agents.

Keywords

Introduction

                             

                       

                         

 

1,2,3-Thiadiazole                  1,2,4-Thiadiazole                   1,2,5-Thiadiazole              1,3,4-Thiadiazole

1,3,4-Thiadiazoles are widely employed as bioisosteric substitutes for heterocyclic rings such as pyrimidine, pyridine, azine, oxadiazole, oxazole, thiazole, and benzene in drug development. This ring system is conjugated, weakly basic, planar, and electron-deficient in nature.³

Thiadiazole derivatives exhibit a broad spectrum of biological activities, including antibacterial, antifungal, insecticidal, antiviral,⁴ Anticancer,⁵ antidiabetic,⁶ antioxidant,⁷ Anticonvulsant effects.⁸

The biological activity of thiadiazoles arises from the strong aromatic nature of their ring structure, which provides greater stability within living systems. Thiadiazoles serve as bioisosteric replacements for the thiazole ring and are also considered bioisosteres of oxadiazole, oxazole, and benzene. Replacing these heterocyclic systems with a thiadiazole ring generally results in analogues with enhanced biological activity, as the presence of sulfur increases lipophilicity.⁹

Antibacterial activity:

Mousa. L. Al-Smadi., synthesized 1,2,3-thiadizole compounds using the hole diffusion method and evaluated for their antimicrobial activity against human pathogenic microorganisms, including gram-positive S. aureus and gram-negative E. coli, local resistant P. aeruginosa and reference pseudomonas aeruginosa and the fungus Candida albicans. The  compound 4-(4-(2-(4-Chloro-3-Methylphenoxy)Ethoxy)Phenyl)-1,2,3-,Thiadiazole (3c) showed the highest activity against C. albicans and was also effective against certain Gram-positive and Gram-negative bacteria, indicating its potential as a novel antibacterial agent.¹⁰

Angelova T. V. et al., reported  4-methyl-1,2,3-thiodiazole compound exhibits antimycobacterial activity against microbacterium tuberculosis. Compound N’-[(E)-(4-hydroxy-3-methoxyphenyl)methylidene]-4-methyl-1,2,3-thiadiazole-5-carbohydrazid (3d) exhibited potent antimycobacterial activity at a submicromolar concentration, showing the lowest MIC value of 0.0730 µM against Mycobacterium tuberculosis H37Rv. Additionally, it demonstrated very low cytotoxicity toward normal human embryonic kidney (HEK-293T) and mouse fibroblast (CCL-1) cell lines.¹¹

Mahendrasingh et al., investigated antibacterial and antifungal activities of all newly synthesized 1,3,4-thiadiazole derivatives were investigated. For antibacterial evaluation, the test organisms included Staphylococcus aureus ATCC 9144, Bacillus cereus ATCC 11778, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 2853. Antifungal activity was assessed using Aspergillus niger ATCC 9029 and Aspergillus fumigatus ATCC 46645.¹²

Umar P. B. et.al.,synthesized 1,3,4-thiadiazole compounds were tested for antibacterial activity using the disc diffusion method against pathogenic bacteria, including Gram-positive strains Staphylococcus aureus (SA) and Bacillus cereus (BC), and Gram-negative strains Escherichia coli (EC) and Pseudomonas aeruginosa (PA). Compounds5-Phenyl-N-(4-(tri?uoromethyl)benzyl)-1,3,4-thiadiazol-2amine (4e) and N-(4-Fluorophenyl)-5-phenyl-1,3,4-thiadiazol-2-amine (4f) exhibited good biological activity.¹³

Joshi D. S. et al., evaluated the antitubercular activity of all the newly synthesized 1,3,4-thiadiazole compounds against the Mycobacterium tuberculosis H37Rv strain using the Microplate Alamar Blue Assay (MABA) method, with pyrazinamide and isoniazid as standard reference drugs. The in vitro results indicate that compounds N-(5-(4-Chlorophenyl)-1,3,4 -oxadiazol-2-yl)-4-(1H-pyrrol1-yl)benzamide (4c), N-(5-(4-Bromophenyl)-1,3,4-oxadiazol-2-yl)-4-(1H-pyrrol1-yl)benzamide (4d), N-(5-(4-Chlorophenyl)-1,3,4-thiadiazol-2-yl)-4-(1H-pyrrol1-yl)benzamide (5c), and N-(5-(4-Bromophenyl)-1,3,4-thiadiazol-2-yl)-4-(1H-pyrrol1-yl)benzamide (5d) showed the highest activity in the series, with an MIC value of 3.12 µg/mL.¹⁴

Rezki N. et al., reported that all newly obtained compounds were tested in vitro for their ability to inhibit the growth of various pathogenic microorganisms, including three Gram-positive bacteria, three Gram-negative bacteria, and three fungal strains. Antimicrobial activity was determined by measuring the minimum inhibitory concentration (MIC) using the broth dilution method. The MIC represents the lowest concentration of a compound that prevents visible microbial growth. Among the tested molecules, diethyl 4,4′-[(1,3,4-thiadiazol-2,5-diyl)bis(sulfanediyl)]dibutanoate (2) and its hydrazide analogue 4,4′-[(1,3,4-Thiadiazol-2,5-diyl)bis(sulfanediyl)]dibutanehydrazide (3) showed notable antibacterial activity against both Gram-positive and Gram-negative organisms with MIC values of 16–31.25 μg/mL, and moderate antifungal effects with MIC values of 31.25–62.5 μg/mL.¹⁵

Antifungal Activity:

Zheng Q. et al., synthesized 5-methyl-1,2,3-thiadiazole derivatives and evaluated their antifungal activity. Fungal growth inhibition was tested using the potato dextrose agar  method against various fungi, including A. solani, B. cinerea, C. arachidicola, C. beticola, C. lagenarium, F. oxysporum, G. zeae, P. triticina, P. infestans, P. piricola, P. sasakii, and R. solani. All compounds showed antifungal activity at 50 μg/mL. Series I compounds were particularly effective, showing over 70% inhibition against B. cinerea and over 60% against P. sasakii. Notably, compound I1 inhibited B. cinerea by 85%, III8 inhibited P. sasakii by 87%, and III1 inhibited P. piricola and P. sasakii by 69% and 65%, respectively.¹⁶

Karaburun Ç. A. et al., evaluated the antifungal activity of synthesized 1,3,4-thiadiazole compounds in vitro against various Candida species, using fluconazole as the reference drug The compounds were tested against C. albicans (ATCC 90028 and ATCC 10231), C. crusei (ATCC 6258), C. parapsilosis (ATCC 22019), C. tropicalis (ATCC 13803), C. glabrata (ATCC 2001), C. famata, and C. lusitaniae. Among the series, compounds 2-((5-((4-Chlorophenyl)amino)-1,3,4-thiadiazol-2-yl)thio)-1-(2,4-difluorophenyl)ethan-1-one(3k) and 2-((5-((4-Chlorophenyl)amino)-1,3,4-thiadiazol-2-yl)thio)-1-(2,4-dichlorophenyl)ethan-1-one (3l) exhibited outstanding antifungal activity against all tested strains, with compound 3l showing the highest potency against C. albicans ATCC 10231. The enhanced antifungal effects of compounds 3k and 3l are attributed to the presence of fluoro and chloro substituents at the second position of the phenyl ring. Moreover, all synthesized compounds demonstrated favorable predicted pharmacokinetic profiles.¹⁷

Caixia W. et al., synthesized thiourea derivatives containing the 1,3,4-thiadiazole moiety (compounds 4a–4r) were evaluated for their antifungal activity against phytopathogenic fungi. Four representative fungi from the Chinese agroecosystem—Curvularia lunata, Cotton Fusarium wilt, P. P. var. nicotianae, and Fusarium spp.—were selected for screening. The commercial fungicide triadimefon was used as the reference standard. The results indicate that most of the compounds (N-Ethyl-N'-[5-(ethylthio)-1,3,4-thiadiazol-2-yl]-thiourea 4a– N-(4-Trifluoromethylphenyl)-N′-[5-(allylthio)-1,3,4- thiadiazol-2-yl]-thiourea 4r) display notable antifungal activity.¹⁸

 Zhou Y. et al., conducted Preliminary in vitro antifungal studies of compounds Y1–Y22 were conducted against ten pathogenic fungal strains. A total of 22 flavonol derivatives containing a 1,3,4-thiadiazole moiety were designed and synthesized, and their structures were confirmed using NMR and HRMS analyses. The antifungal evaluation revealed that compound 4-((3-(thiazol-2-ylthio)propyl)oxy)-3-(3-fluorophenyl)-2H-chromen-2-one (Y18) exhibited strong activity against B. cinerea, with an EC?? value of 2.4 μg/mL, which was significantly better than that of azoxystrobin (21.7 μg/mL).¹⁹

Zoumpoulakis P. et al., reported that the synthesized compounds displayed strong antifungal activity, with MIC values of 0.06–0.50 μmol/mL and MFC values of 0.07–0.75 μmol/mL. They were generally more potent than ketoconazole and bifonazole, except compound N-{5-[2-(N-Dimethylsulfamoyl)-4,5-dimethoxy-benzyl]-1,3,4-thiadiazol-2-yl}-N-isopropylamine( 4d), which was slightly less active against a few fungal strains. Compound N-{5-[2-(N-Dimethylsulfamoyl)-4,5-dimethoxy-benzyl]-1,3,4-thiadiazol-2-yl}-N-butylamine (4e). showed the highest activity. Fulvia fulvum was the most sensitive fungus, while Aspergillus versicolor was the most resistant. Overall, the thiadiazole derivatives demonstrated significantly superior antifungal activity, reaching 8–10 times higher potency in certain cases.²⁰

Insectisidal Activity:

Wang H. et al.,synthesized two series of target compounds—one containing a benzoyl ring and the other incorporating a 5-methyl-1,2,3-thiadiazole ring adjacent to a tert-butyl group. At 200 μg/mL, both series showed similar insecticidal activity against P. xylostella, though compounds 4-methyl-1,2,3-thiadiazole-5-carbonyl chloride (VII) exhibited stronger effects.²¹

Suzuki J. et al., evaluated the insecticidal activities of seven 1,2,4-oxadiazoles and twenty-five 1,2,4-thiadiazoles were tested against N. lugens, N. cincticeps, and A. craccivora. Both 1,2,4-thiadiazole derivatives [Methyl-5-(3-pyridyl)-1,2,4-thiadiazole (7m-2 )and 3-Methyl-5-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,4-thiadiazole(9m-2) ]showed very low inhibition of EPI binding to membranes, with nAChR binding activities below 10%. This indicates that these compounds display nearly identical insecticidal effects on both imidacloprid-resistant and susceptible strains of N. lugens.²²

Dong Lia Yue et al., designed and synthesized novel 1,2,4-triazole-containing 1,2,3-thiadiazole derivatives and evaluated their insecticidal activity against Aphis laburni using the leaf-dip method.  In addition, the antiviral activity against TMV was examined under both curative and induction models following established literature methods.²³

Madkour H. F. et al.,synthesized several thiadiazole derivatives using readily available starting materials. The insecticidal potential of the newly obtained compounds was evaluated against 4th instar larvae of Spodoptera littoralis, and most of them displayed good activity. Compound 7-Amino-2-(2-chlorophenyl)-5-(4-chlorophenyl)-5H-[1,3,4]thiadiazolo [3,2-a]pyrimidine-6-carbonitrile (8) showed the highest potency, exhibiting the lowest LC?? value of 114.99 ppm.²⁴

Antiviral activity:

Dong Li Wei et al., synthesized acrylamide derivatives containing a 1,2,3-thiadiazole moiety were evaluated in vitro for their cytotoxic and anti-HBV activities in 2.2.15 cells, with lamivudine used as the reference antiviral drug. Among all the tested compounds, N-(1-bromo-1-(4-chlorophenyl)-3-oxo-3-(piperidin-1-yl)prop-1-en-2-yl)-4-methyl-1,2,3-thiadiazole-5-carboxamide (9c) exhibited the strongest anti-HBV activity, showing an IC?? value of 3.59 μg/mL, which was approximately three times higher than that of the standard drug lamivudine.²⁵

Fujiwara M. et al., identified TDA derivatives as novel HIV-1 specific non-nucleoside reverse transcriptase inhibitors (NNRTIs), though their high lipophilicity and strong plasma protein binding limited effectiveness. To address this, a new series was synthesized, and one compound, N-methyl-N-propyl O-[3,5-dichloro-2-amino-4-(1,3,4-thiadiazol-2-yl)phenyl] carbamate (RD4-2217), showed strong inhibition of multiple HIV-1 strains with reduced lipophilicity and protein binding. Its antiviral evaluation is ongoing in the presence of increasing human serum concentrations.²⁶

Hu Yuzhi et al., synthesized twenty-one coumarin derivatives containing 1,3,4-oxadiazole or 1,3,4-thiadiazole moieties and evaluated their antiviral activities.among them,  compound N-(5-((2-hydroxy-3-((2-oxo-2H-chromen-4-yl)oxy)propyl)thio)-1,3,4-thiadiazol-2-yl)-4-methylbenzamide(Y5) exhibited the higher antiviral activity at a concentration of 500 μg/mL.( EC50 =218.6 μg/mL).²⁷

Brai A. et al.,designed and synthesized novel 1,3,4-thiadiazole derivatives as inhibitors of DDX3X to evaluate their antiviral activity. The antiviral potential was assessed using a phenotypic assay known as the BiCycle Assay, which measures the half-maximal inhibitory concentration (IC??) against the HIV-1 wild-type reference strain NL4-3 in TZM-bl cells. The compound2-(2-(4-hydroxyphenyl)-1,3,4-thiadiazol-5-yl)isoindoline-1,3-dione (24) demonstrated the strongest anti-HIV-1 effect, showing an IC?? of 2.8 µM.²⁸

Yu Lu et al., evaluated the antiviral effects of the synthesized compounds against cucumber mosaic virus (CMV) using the half-leaf method. Several of the compounds demonstrated notable in vivo activity, with compounds (2E)-3-(2,4-dimethoxyphenyl)-1-(4-hydroxyphenyl)-2-((phenylthio)imino)-3-(thiophen-2-yl)prop-1-en-1-one(4e) and (2E)-3- (3,4-dimethoxyphenyl)-1-(thiophen-2-yl)prop-2-en-1-one) (4f) showing particularly strong curative effects of 55.9% and 50.2%, respectively—both higher than ribavirin (36.8%). In contrast, the compounds displayed protective and inactivation activities comparable to those of ribavirin.²⁹

Anticancer activity:

Chidella K. et al., synthesized 1,2,4-thiadiazole-linked imidazo[1,2-b]pyridazine (10a–j) derivatives were tested for their anticancer potential against four human cancer cell lines — breast (MCF-7), lung (A549), prostate (DU-145), and breast (MDA-MB-231) — using the MTT assay. An initial structure–activity relationship (SAR) analysis revealed that compound 2-(3-(3,4,5-Trimethoxyphenyl)-1,2,4-thiadiazol-5-yl)-3-(thiophen-2-yl)imidazo[1,2 b]pyridazine(10b), bearing a 3,4,5-trimethoxy group on the phenyl ring attached to the thiadiazole core, exhibited the most potent activity, with IC?? values of 0.09 ± 0.0076 µM (MCF-7), 0.012 ± 0.002 µM (A549), 0.017 ± 0.0041 µM (DU-145), and 0.034 ± 0.0053 µM (MDA-MB-231).³⁰

Trafalis T. D. et al. reported the evaluation of novel triazolo[3,4-b][1,3,4]thiadiazole derivatives for anticancer potential, where compounds KA39, 2-((6-(2,5-dinitrophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl)methyl)-N,N-diethyl4,5 dimethoxybenzenesulfonamide (6e), and 2-((6-(2,5-dinitrophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl)methyl)-N,N-diisopropyl4,5-dimethoxybenzenesulfonamide(7d) 7d showed the strongest activity against several human cancer cell lines, with KA39 being the most effective. The presence of a 2,5-dinitrophenyl group at the C-6 position was found to be crucial for enhanced activity. Furthermore, in vivo studies revealed low acute toxicity and marked tumor growth inhibition (~62–68%) in an HT-29 xenograft model, underscoring KA39, KA25, and KA26 as promising anticancer leads.³¹

Sudhakar S. G. D. et al., synthesized 1,2,4-thiadiazole derivatives containing a 1,2,4-oxadiazole moiety were evaluated for their anticancer potential against four human cancer cell lines—MCF-7 (breast), A549 (lung), Colo-205 (colon), and A2780 (ovarian)—using the MTT assay. Etoposide served as the reference drug. Most of the compounds exhibited moderate to strong    anticancer activity, with IC?? values ranging from 0.10 ± 0.02 to 22.1 ± 5.76 μM, compared to the positive control (IC?? = 0.13 ± 0.017 to 3.08 ± 0.135 μM).³²

Mhaidat M. N. et al. evaluated the acute cytotoxicity of 1,2,3-thiadiazole and 1,2,3-selenadiazole compounds against several cancer cell lines,breast (HMT3522, MCF7), colorectal (SW480, HCT116), and melanoma (MV3, C32)—using the MTT assay. Compound 1-(1,2,3-selenadiazole-4-yl)carbaldehyde (4b) showed activity against all tested tumor cell lines, with IC?? values ranging from 52.17 to 114.79 µg/mL. In comparison, 1,3,5-tris(1,2,3-thiadiazole-4-yl)benzene (4c) exhibited stronger cytotoxic effects across all cancer cell lines.³³

Shaikh A. S. et al., reported the synthesis of a new series of 1,3,4-substituted thiadiazole derivatives (8b–g) obtained from 4-substituted thiazol-2-chloroacetamides (4b–g) and characterized using FT-IR, ¹H NMR, ¹³C NMR, and mass spectrometry. The synthesized compounds (8a–g) were evaluated for their in vitro anticancer activity against hepatocellular carcinoma (HepG-2), lung carcinoma (A549), breast carcinoma (MCF-7), and pseudo-normal embryonic liver (L02) cell lines using the MTT assay. Among them, compounds 2-Chloro-N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]acetamide (4j) and 2-[(5-amino-1,3,4-thiadiazol-2-yl)thio]-N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]acetamide (8d) showed the highest anticancer potency, with GI?? values of 1.82, 2.61, 2.38 µM and 2.98, 2.85, 2.53 µM against MCF-7, A549, and HepG-2 cells, respectively, comparable to doxorubicin.³⁴

Janowska S.et al., discovered and synthesized new thiosemicarbazide and 1,3,4-thiadiazole derivatives, which were evaluated for their in vitro anticancer activity against two breast cancer cell lines using the MTT assay and DNA biosynthesis analysis. The results showed that all compounds displayed dose-dependent cytotoxicity toward MCF-7 and MDA-MB-231 cells, with compound 2-(2-Trifluorometylophenylamino)-5-(3-methoxyphenyl)-1,3,4-thiadiazole (ST10) showing the highest activity against MCF-7 (IC?? = 49.6 µM).³⁵

Dawood M. K. et al. confirmed the structures of the newly synthesized 1,3,4-thiadiazole derivatives using elemental and spectral analyses.  Selected compounds were evaluated for anticancer activity against the HCT-116 colon carcinoma cell line, and their structure–activity relationship (SAR) was examined. Compounds 5-(4-Chlorophenyl)-N-(3,5-diphenyl-1,3,4-thiadiazol-2(3H) ylidene)-1,3,4-oxadiazol-2-amine (6), 1-(5-((5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl)imino)-4-phenyl 4,5-dihydro-1,3,4-thiadiazol-2-yl)ethanone (13a) and 5-((5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl)imino)-N,4 diphenyl-4,5-dihydro-1,3,4-thiadiazole-2-carboxamide (19a) showed weak inhibitory effects on HCT-116 cells, with IC?? values of 9 μg/mL.³⁶

Antidiabetic activity:

Hussain R. et al., reported the synthesis of a series of hybrid 1,3,4-thiadiazole–fused–1,2,4-thiadiazole derivatives incorporating a 1,4-benzodioxine ring, which were subsequently evaluated for their in vitro α-amylase and α-glucosidase inhibitory activities. All the synthesized analogs exhibited notable inhibitory potency toward both enzymes, with IC?? values ranging from 0.70 ± 0.01 to 30.80 ± 0.80 μM for α-amylase and 0.80 ± 0.01 to 29.70 ± 0.40 μM for α-glucosidase, demonstrating activity comparable to or exceeding that of the standard drug acarbose.³⁷

Khan S. et al., reported that diabetes mellitus (DM), caused by the harmful activity of α-amylase and α-glucosidase enzymes, is commonly treated with enzyme inhibitors that often have side effects. To find safer alternatives, 17 benzimidazole-based thiadiazole derivatives were synthesized and tested. These compounds showed significant inhibitory activity against both enzymes, with IC?? values ranging from 1.10 to 24.20 µM for α-amylase and 2.10 to 26.10 µM for α-glucosidase, depending on the substituents on the aromatic ring.³⁸

Shulgau Z. et al., evaluated sulfur-containing derivatives, particularly thiadiazole heterocycles,compounds 5′–9′a–c were screened for their potential antidiabetic activity based on their ability to inhibit α-glucosidase enzyme activity.. The results revealed that these compounds exhibited significantly higher inhibitory effects compared to the reference drug acarbose (49.5%). Notably, compound 2-(5-((6-Methyl-2-oxo-4-phenyl-1,2-dihydropyridin-3-yl)carbamoyl)-1,3,4-thiadiazol-2 yl)benzoic acid (9′b) demonstrated an IC?? value of 3.66 mM, which is approximately 3.7 times lower than that of acarbose (IC?? = 13.88 mM), indicating superior α-glucosidase inhibitory potency.³⁹

Datar A. P. et al., reported both in vitro and in vivo evaluations of the synthesized of thiadiazole compounds. In the in vitro study using porcine α-amylase, N-(5-(4-nitrophenyl)-1,3,4-thiadiazol-2-yl) acetamide(TD1) showed the highest activity, while acarbose was used as the standard α-glucosidase inhibitor. Acarbose reduces glucose absorption by slowing carbohydrate digestion and may help prevent or delay diabetic symptoms. The pancreatic α-amylase inhibition results showed that only 2-(5-phenyl-1,3,4-thiadiazol-2-ylamino)-N-ptolylacetamide(TD7) exhibited activity comparable to acarbose. In the in vivo study on alloxan-induced diabetic rats, TD1, N-(4-nitrobenzilidene)-5-phenyl-1,3,4- thiadiazol-2-amine(TD2), and TD7 significantly lowered blood glucose levels at a dose of 35 mg/kg (p.o.). Considering both in vitro and in vivo findings, TD7 emerged as the most promising compound.⁴⁰

CONCLUSION

Thiadiazole derivatives represent a versatile and pharmacologically important class of heterocyclic compounds. Their strong aromaticity, bioisosteric behavior, and sulfur-induced lipophilicity contribute to enhanced biological activity across diverse therapeutic and agricultural applications. The consistent demonstration of potent antibacterial, antifungal, antiviral, insecticidal, anticancer, and antidiabetic activities underscores the thiadiazole scaffold as a valuable lead structure for drug discovery. Further optimization, structure–activity relationship studies, and in vivo evaluations are expected to facilitate the development of safe and effective thiadiazole-based agents for future medicinal and agrochemical use.

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