Mechanism-based approaches of 1,3,4 thiadiazole scaffolds as potent enzyme inhibitors for cytotoxicity and antiviral activity

Kumar, Davinder; Kumar, Harsh; Kumar, Virender; Deep, Aakash; Sharma, Aastha; Marwaha, Minakshi Gupta; Marwaha, Rakesh Kumar

doi:10.1016/j.medidd.2022.100150

Cited by 19 publications

(17 citation statements)

References 114 publications

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“…Melting points were determined via an open capillary method using a STUART SMP3 (BIBBY STERILIN, UK). The 1 H and 13 C NMR spectra were recorded using an Avance AV500 Spectrometer (Bruker, Germany) at 500 MHz and 150 MHz, respectively, using DMSO-d 6 as the solvent and TMS as an internal standard. ESI-mass spectra were recorded using an LC-MS LTQ Orbitrap XL, ESI/HR-mass spectra were recorded using Thermo Scientific Exactive Plus Orbitrap spectrometers (ThermoScientific, USA) in methanol using the ESI method.…”

Section: Methodsmentioning

confidence: 99%

“…This isothiocyanate derivative was prepared from p-toluene sulfonyl chloride by reaction with ammonium thiocyanate in dried acetonitrile in the presence of pyridine as a base (Scheme 1). The synthesized sulfonyl thiourea compounds were characterized using 1 H NMR, 13 C NMR, and mass spectroscopic methods (see ESI †). All these obtained thioureas were soluble in a mixture of ethanol and/ or toluene (1 : 1 by volume), and could not be dissolved in water.…”

Section: Chemistrymentioning

confidence: 99%

“…4,12 Currently, numerous drugs containing a 1,3,4-thiadiazole ring are in clinical trials. 13 For example, sulfamethizole, a thiadiazole derivative, has been used as an antimicrobial agent. 14 Acetazolamide is used in the treatment of glaucoma, drug-induced edema, heart-failure-induced edema, epilepsy and reducing intraocular pressure after surgery.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, biological and molecular modelling for 1,3,4-thiadiazole sulfonyl thioureas: bacterial and fungal activity

Dinh Thanh,

Ngoc Toan,

Thi Kim Giang

et al. 2023

RSC Med. Chem.

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Section: Methodsmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis, biological and molecular modelling for 1,3,4-thiadiazole sulfonyl thioureas: bacterial and fungal activity

Dinh Thanh,

Ngoc Toan,

Thi Kim Giang

et al. 2023

RSC Med. Chem.

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“…The 1,3,4‐thiadiazoles are known to exhibit a wide range of biological actions such as antifungal, anticancer, antibacterial, anti‐leishmanial, antitubercular, antioxidative, and antidiabetic agents. [ 43–48 ] Additionally, they serve as the initial building blocks for the production of many different kinds of chemical compounds, including sulfa medicines, fungicides, dyes, and catalysts for chemical reactions. Megazol (antiparasitic), acetazolamide (carbonic anhydrase inhibitor), methazolamide (diuretic), sulfamethizole (antibacterial sulfonamide), and Cefazolin (first‐generation cephalosporin) are some of the most well‐known thiadiazole‐containing medications in the market (Figure 2).…”

Section: Introductionmentioning

confidence: 99%

“…The 1,3,4-thiadiazoles are known to exhibit a wide range of biological actions such as antifungal, anticancer, antibacterial, anti-leishmanial, antitubercular, antioxidative, and antidiabetic agents. [43][44][45][46][47][48] Additionally, they serve as the initial building blocks for the production of many different kinds of chemical compounds, including sulfa medicines, F I G U R E 1 Some drugs containing 1,3,4-thiadiazole and 1,2,3-triazole scaffolds. fungicides, dyes, and catalysts for chemical reactions.…”

mentioning

confidence: 99%

Synthesis of 1,2,3‐triazole‐1,3,4‐thiadiazole hybrids as novel α‐glucosidase inhibitors by in situ azidation/click assembly

Kumar

Dhameja

Kurella

et al. 2023

Archiv der Pharmazie

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α-Glucosidase inhibition is widely used in the oral management of diabetes mellitus (DM), a disease characterized by high blood sugar levels (hyperglycemia) and abnormal carbohydrate metabolism. In this respect, a series of 1,2,3-triazole-1,3,4thiadiazole hybrids 7a-j were synthesized, inspired by a copper-catalyzed one-pot azidation/click assembly approach. All the synthesized hybrids were screened for inhibition of the α-glucosidase enzyme, displaying IC 50 values ranging from 63.35 ± 0.72 to 613.57 ± 1.98 μM, as compared to acarbose (reference) with IC 50 of 844.81 ± 0.53 μM. The hybrids 7h and 7e with 3-nitro and 4-methoxy substituents at the phenyl ring of the thiadiazole moiety were the best active hybrids of this series with IC 50 values of 63.35 ± 0.72 μM, and 67.61 ± 0.64 μM, respectively. Enzyme kinetics analysis of these compounds revealed a mixed mode of inhibition. Moreover, molecular docking studies were also performed to gain insights into the structure-activity-relationships of the potent compounds and their corresponding analogs.

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An efficient eco-friendly, simple, and green synthesis of some new spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives as potential inhibitors of SARS-CoV-2 proteases: drug-likeness, pharmacophore, molecular docking, and DFT exploration

El-Saghier,

Enaili,

Abdou

et al. 2023

Mol Divers

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Introduction The coronavirus disease 2019 (COVID-19) pandemic has caused a global health crisis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that can cause severe respiratory illness. There is no specific treatment for COVID-19, and the development of new drugs is urgently needed. Problem statement The SARS-CoV-2 main protease (Mpro) enzyme is a critical viral enzyme that plays a vital role in viral replication. The inhibition of Mpro enzyme can be an effective strategy for developing new COVID-19 drugs. Methodology An efficient operationally simple and convenient green synthesis method had been done towards a series of novel spiro-N-(4-sulfamoylphenyl)-2-carboxamide derivatives, in ethanol at room temperature in green conditions, up to 90% yield. The molecular structures of the synthesized compounds were verified using spectroscopic methods.The title compounds were subjected to in silico analysis, including Lipinski’s rule and ADMET prediction, in addition to pharmacophore modeling and molecular docking against the active site of SARS-CoV-2 target main protease (Mpro) enzyme (6LU7). Furthermore, both of the top-ranked compounds (5 and 6) and the standard Nirmatrelvir were subjected to DFT analysis. Findings The synthesized compounds exhibited good binding affinity to SARS-CoV-2 Mpro enzyme, with binding energy scores ranging from − 7.33 kcal/mol (compound 6) and − 7.22kcal/mol (compound 5) to − 6.54 kcal/mol (compounds 8 and 9). The top-ranked compounds (5 and 6) had lower HOMO–LUMO energy difference (ΔE) than the standard drug Nirmatrelvir. This highlights the potential and relevance of charge transfer at the molecular level. Recommendation These findings suggest that the synthesized spiro-N-(4-sulfamoylphenyl)-2-carboxamide derivatives could be potential candidates for COVID-19 drug development. To confirm these drugs' antiviral efficacy in vivo, more research is required. With very little possibility of failure, this proven method could aid in the search for the SARS-CoV-2 pandemic's desperately needed medications. Graphical abstract

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Mechanism-based approaches of 1,3,4 thiadiazole scaffolds as potent enzyme inhibitors for cytotoxicity and antiviral activity

Cited by 19 publications

References 114 publications

Synthesis, biological and molecular modelling for 1,3,4-thiadiazole sulfonyl thioureas: bacterial and fungal activity

Synthesis, biological and molecular modelling for 1,3,4-thiadiazole sulfonyl thioureas: bacterial and fungal activity

Synthesis of 1,2,3‐triazole‐1,3,4‐thiadiazole hybrids as novel α‐glucosidase inhibitors by in situ azidation/click assembly

An efficient eco-friendly, simple, and green synthesis of some new spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives as potential inhibitors of SARS-CoV-2 proteases: drug-likeness, pharmacophore, molecular docking, and DFT exploration

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