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

Abstract

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

Synthesis, docking and biological evaluation of purine-5-N-isosteresas anti-inflammatory agents

“…As part of our ongoing research into the synthesis of novel heterocycles, [42][43][44][45][46][47][48][49][50][51][52] we prepared in this article a new series of 5-amino-7-(substituted)-N-(4-sulfamoylphenyl)-4,7-dihydro- [1,2,4] triazolo[1,5-a][1,3,5]triazine-2-carboxamidederivatives 4-13 by a new method, a smooth way, one-pot reaction, energy saving (at room temperature), low cost (without catalyst), short period (about 3 h), green solvent (EtOH) method, with high yields (79-93%) and no requirements for toxic chemicals, which follow the green synthesis rules. Thiocarbohydrazide 1 was allowed to react with cyanoguanidine 2 and various aldehydes 3a-3j, namely, furfural, 2-methylbenzaldehyde, cinnamaldehyde, glyoxal, 2-chlorobenzaldehyde, 4-methoxybenzaldehyde, 1naphthaldehyde, 2-hydroxybenzaldehyde, 4(N,N)-dimethyl benzaldehyde, and 3-hydroxybenzaldehyde.…”

Thiadiazole/Thiadiazine Derivatives as Insecticidal Agent: Design, Synthesis, and Biological Assessment of 1,3,4-(Thiadiazine/Thiadiazole)-Benzenesulfonamide Derivatives as IGRs Analogues against Spodoptera littoralis

“…Thus, the authors report the findings from an evaluation of the bioinsecticidal activity of these recently synthesized compounds. In this work, we used 2-hydrazinyl- N -(4-sulfamoylphenyl)-2-thioxoacetamide as starting material which allowed to react with various electrophile reagents to create novel cyclized thiadiazole/thiadiazine moiety bearing sulfamoylcarboxamide group with a variety of substitutions at position. Additionally, the insecticidal efficacy of the synthesized compounds was examined using the second and fourth instars of S.…”

“…The synthesis of insecticidal drugs has focused a great deal of research on tiny compounds containing a heterocyclic moiety with five or six members, specially 1,3,4-thiadiazole and 1,3,4-thiadiazine. − Because of its physiological activity, 1,3,4-thiadiazole is becoming increasingly important in medicinal chemistry. These agents include those that are anticonvulsant, anti-Alzheimer, anticancer and antitumor, antidiabetic, antiviral, antiplatelet, antituberculosis, carbonic anhydrase inhibitor agents, and diuretic agents .…”