Isatin Derivatives Research Articles

İsatinin HepG2 ve AML12 hücre hatları üzerindeki moleküler etkilerinin araştırılması

Isatin is an indole-derived organic compound. It is a natural component of the Couroupita guianensis plant. It is also the metabolic derivative of the human body hormone adrenaline. Studies have shown the anti-tumoral effects of isatin derivatives. In this study, the cytotoxic effects of isatin on HepG2, a hepatocellular cancer cell line was investigated. Additionally, its cytotoxic and protective-proliferative effects on AML12, a healthy liver cell line was investigated. This evaluation was conducted using MTT, fluorescent staining, wound healing, and real-time polymerase chain reaction analyses. The IC50 values for 48 hours of isatin application were calculated as 186.23 µM for HepG2 and 7.05 mM for AML12. The analysis of wound healing and fluorescent staining at varying doses of HepG2 application revealed suppression of proliferation and triggered apoptosis in HepG2 cells. In contrast, AML12 cells exhibited promoted proliferation under similar conditions. Moreover, the observed upregulation of oxidative stress genes CuZn/Mn-SOD and mitochondrial apoptotic pathway genes Bax, cleaveled-Cas3, APAF1, and p53 in HepG2 cells contrasted with their decreased expression in AML12 cell lines. These results suggest the potential of natural isatin as a promising anti-cancer agent for liver cancer cell lines and as a protective supplement for healthy liver cells.

Design, synthesis, insilco study and biological evaluation of new isatin-sulfonamide derivatives by using mono amide linker as possible as histone deacetylase inhibitors.

Aim: To evaluate the cytotoxic activity of newly synthesized a series of novel HDAC inhibitors comprising sulfonamide as zinc binding group and Isatin derivatives as cap group joined by mono amide linker as required to act as HDAC inhibitors. Materials and Methods: The utilization of sulfonamide as zinc binding group joined by N-alkylation reaction with ethyl-bromo hexanoate as linker group that joined by amide reaction with Isatin derivatives as cap groups which known to possess antitumor activity in the designed of new histone deacetylase inhibitors and using the docking and MTT assay to evaluate the compounds. Results: Four compounds have been synthesized and characterized successfully by ART-FTIR, NMR and ESI-Ms. the compounds were synthesized and characterized by successfully by ART-FTIR, NMR and ESI- Ms. Assessed for their cytotoxic activity against human colon adenocarcinoma MCF-7 (IC50, I=105.15, II=60.00, III=54.11, IV=56.57, vorinostat=28.41) and hepatoblastoma HepG2 (IC50, I=63.91, II=135.18, III=118.85, IV=51.46, vorinostat=37.50). Most of them exhibited potent HDAC inhibitory activity and significant cytotoxicity. Conclusions: The synthesized compounds (I, II, III and IV) showed cytotoxicity toward MCF-7 and HepG2 cancer cell lines and their docking analysis provided a preliminary indication that they are viable [HDAC6] candidates.

Green synthesis and in-vitro screening of 3-((4-(arylideneamino)phenyl) imino)indolin-2-one derivatives antimycobacterial agents

In this research article, we attempted to synthesize some new isatin derivatives, 3-((4-(arylideneamino)phenyl)imino)indolin-2-ones (2a-2g) by Schiff\'s base reaction under microwave technique. The structural characterizations of synthesized compounds were done by using different analytical techniques such as IR, 1HNMR, mass spectrometry, and elemental analysis. We aim to develop new compounds with improved antimycobacterial activities. These title compounds were screened for their antimycobacterial activity against the Mycobacterium tuberculosis H37Rv strain by using the microplate Alamar blue dye assay (MABA) method. All title compounds showed significant antimycobacterial activity. Compound 2g was found most potent compound with a MIC value of 6.25 µg/mL among all tested compounds when compared with standard drugs streptomycin (6.25µg/mL) and isoniazid (6.25 µg/mL).

A novel, effective, green and recyclable α-Fe2O3@MoS2@Ni Magnetic nanocatalyst in preparation of a series of 1,2,4-triazolidine-3-thiones and spiro-triazole hybrids

In current paper, a novel, green, efficient and recyclable magnetic nanocatalyst (α-Fe2O3@MoS2@Ni) was prepared and characterized by spectroscopic and microscopic techniques (FT-IR, XRD, SEM, EDX, TEM and VSM). α-Fe2O3@MoS2@Ni magnetic nanoparticles (MNPs) were utilized for preparation of 1,2,4-triazolidine-3-thiones and spiro-triazole hybrid series. In this method, a series of triazole derivatives prepared from the reaction between thiosemicarbazide or semicarbazide with diverse isatine derivatives or various arylaldehydes and ketones at room temperature in water as solvent with great yields and short reaction times. α-Fe2O3@MoS2@Ni MNPs was simply removed from the reaction mixture and was reused for five times without any notable changes in its catalytic activity.

Novel N-heterocyclic Schiff base based on Isatin derivative as a sustainable, eco-friendly, and highly efficiency corrosion inhibitor for carbon steel in sulfuric acid medium: Electrochemical and Computational investigation

The present study aimed to synthesize and investigate the inhibitory effects of two novel Schiff bases namely: (Z)− 1-(5-nitro-2-oxoindolin-3-ylidene) semicarbazide (NOSC) and Z)− 1-(5-nitro-2-oxoindolin-3-ylidene) thiosemicarbazide (NOTSC) for carbon steel (CS) corrosion in 0.5 M H2SO4 medium. Through chemical and electrochemical investigations, the efficiency of NOSC and NOTSC's corrosion inhibition was ascertained experimentally at 298 K. It is noteworthy that the inhibitory efficacy of NOTSC and NOSC reached 93.4% and 91.6%, respectively, at a concentration of 10−3 M. Studies using potentiodynamic polarization revealed that NOTSC and NOSC functioned as mixed-type inhibitors. A depressed capacitive loop with varying concentrations is the primary way that the Nyquist plot of impedance is represented. The transportation of corrosive ions to the metal substrate is impeded by the adsorption of both NOSC and NOTSC, as determined by the Langmuir isotherm. Apart from the chemical and electrochemical investigations, additional insights were gained into the inhibitory mechanism by the application of density functional theory (DFT), molecular dynamics simulation (MDS), and an understanding of the molecular structure of NOTSC and NOSC. A robust correlation was discovered between the theoretical and experimental results through the application of DFT/MDS computational study.

Eco-friendly K-10 Clay-Mediated [3 + 3] Spiroannulation of Morita-Baylis-Hillman Adduct of Isatin with Anthracene: Synthesis of Green Fluorophore Compounds.

An easy and simple spiroannulation of the Morita-Baylis-Hillman adduct of isatin derivatives with anthracene was achieved in moderate-to-good yields (37-75%). The spiroderivatives synthesized in this work exhibited green fluorescence properties. The reaction occurred in metal-free eco-friendly K-10 clay-mediated conditions. The final products have multiple structural features such as 3-spirooxindole, fluorophoric anthracene, phenanthracene, phenalene, and perylene cores.

Integrated control strategies for dengue, Zika, and Chikungunya virus infections.

Arboviruses are a major threat to public health in tropical regions, encompassing over 534 distinct species, with 134 capable of causing diseases in humans. These viruses are transmitted through arthropod vectors that cause symptoms such as fever, headache, joint pains, and rash, in addition to more serious cases that can lead to death. Among the arboviruses, dengue virus stands out as the most prevalent, annually affecting approximately 16.2 million individuals solely in the Americas. Furthermore, the re-emergence of the Zika virus and the recurrent outbreaks of chikungunya in Africa, Asia, Europe, and the Americas, with one million cases reported annually, underscore the urgency of addressing this public health challenge. In this manuscript we discuss the epidemiology, viral structure, pathogenicity and integrated control strategies to combat arboviruses, and the most used tools, such as vaccines, monoclonal antibodies, treatment, etc., in addition to presenting future perspectives for the control of arboviruses. Currently, specific medications for treating arbovirus infections are lacking, and symptom management remains the primary approach. However, promising advancements have been made in certain treatments, such as Chloroquine, Niclosamide, and Isatin derivatives, which have demonstrated notable antiviral properties against these arboviruses in vitro and in vivo experiments. Additionally, various strategies within vector control approaches have shown significant promise in reducing arbovirus transmission rates. These encompass public education initiatives, targeted insecticide applications, and innovative approaches like manipulating mosquito bacterial symbionts, such as Wolbachia. In conclusion, combatting the global threat of arbovirus diseases needs a comprehensive approach integrating antiviral research, vaccination, and vector control. The continued efforts of research communities, alongside collaborative partnerships with public health authorities, are imperative to effectively address and mitigate the impact of these arboviral infections on public health worldwide.

Synthesis biological evaluation and molecular docking of isatin hybrids as anti-cancer and anti-microbial agents

Isatin, known as 1H-indole-2,3-dione, was originally recognised as a synthetic molecule until its discovery in the fruits of the cannonball tree, Couroupita guianensis. It is naturally occurring in plants of the genus Isatis and serves as a metabolic derivative of adrenaline in humans. Isatin possesses significant pharmacological importance, and its synthetic versatility has prompted extensive interest in its derivative compounds due to their diverse biological and pharmacological properties. These derivatives represent a valuable class of heterocyclic compounds with potential applications as precursors for synthesizing numerous valuable drugs. In the pursuit of advancing our research on isatin hybrids, we investigate the utilisation of readily available hydrazonoindolin-2-one and isatin as starting materials for the synthesis of a wide range of analogues. Characterisation of the synthesized compounds was carried out through various analytical techniques. Furthermore, the obtained compounds were subjected to extensive testing to evaluate their anticancer and antimicrobial activities. Specifically, their efficacy against key proteins, namely Staphylococcus aureus protein (PDB ID: 1JIJ), Escherichia coli protein (PDB ID: 1T9U), Pseudomonas aeruginosa protein (PDB ID: 2UV0), and Acinetobacter baumannii protein (PDB ID: 4HKG), was examined through molecular docking calculations. Several molecules, such as 3, 4, 6, 16, and 19, displayed remarkable activity against the renal cancer cell line UO-31. Additionally, the results of antimicrobial activity testing revealed that compound 16 exhibited significant cytotoxicity against Candida albicans and Cryptococcus neoformans. Subsequently, ADME/T calculations were performed to gain insights into the potential effects and reactions of these molecules within human metabolism. This comprehensive study provides valuable insights into the potential pharmacological applications of isatin derivatives and underscores their significance in drug development.

Synthesis, Docking and In Vitro Evaluation of Spiroindoline‐3,2’‐Quinazoline Derivatives

AbstractThe Wang‐OSO3H catalyzed synthesis of a series of spiroindoline‐3,2’‐quinazoline derivatives and their in silico and in vitro evaluation against MtbCM (Mycobacterium tuberculosis Chorismate Mutase) are disclosed. Initially, a library of small molecules based on spiroindoline‐3,2’‐quinazoline framework was constructed. The reaction of 2‐aminobenzamide with appropriate isatin derivatives in the presence of Wang‐OSO3H under ultrasound irradiation was used for this purpose. The reaction proceeded under mild conditions to afford the desired products in good yields within a short duration. With the use of heterogeneous catalyst, inexpensive solvent as reaction media, and ultrasound as the source of green energy the methodology appeared to be a useful alternative to the previously reported methods. The in silico docking of all the synthesized compounds into the MtbCM (PDB: 2FP2) revealed that the binding of these compounds took place on the external surface pockets of the MtbCM active site cavity mainly in two different clusters. Three compounds that interacted well with MtbCM also showed good (57–64 %) inhibition of MtbCM in vitro when tested at 10 μM. Based on in silico and in vitro studies along with the ADME predictions these three spiroindoline‐3,2’‐quinazoline derivatives were identified as pre‐hits.

Entropy controlled reaction of piperidine with isatin derivatives in 80% aqueous methanol

The reactions of 5- and 7-substituted isatin derivatives (H, Me, Cl, Br) with piperidine in 80% aqueous methanol gave the corresponding 1-(2’-amino-5’- or 3’- substituted phenyl)-2-(piperidin-1-yl) ethane-1,2-dione derivatives. The reaction is proceeded through nucleophilic attack on C-2 followed by ring opening process. The reaction showed a second order and the isokinetic temperature is 169 K indicating that the reaction is entropy controlled. The constant ∆G# value, the linear plot of ∆H# versus ∆S#, plot of log kN values at high temperature versus those at low temperatures indicated that a unified mechanism of the reactions for all substituents. The σo-Taft's constants are linearly correlated with log kN values and the ρ values are (2.01–1.86) pointing out that inductive effect of substituent is predominant and the rate-limiting is the breakdown of the tetrahedral intermediate T− and the ring opening is catalyzed by water.

Design, Synthesis and Evaluation of Schiff base derivatives of Isatin as Antibacterial agents

A novel series of Schiff bases derivatives of isatin has been designed, synthesized, and evaluated for antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). The binding mode of the designed compounds was investigated in the active site of enzyme peptide deformylase of E.coli and S. aureus respectively. Eighteen compounds were designed based on a literature review and docked against peptide deformylase catalytic cavity. All new compounds were tested for in vitro antibacterial activity against a variety of Gram positive and Gram-negative bacterial strains, such as S. aureus and E. coli, using the broth dilution method standard using actinonin and quercetin as references. The compound-14 and 5 showed the highest mol dock score in the docking study as well as good in vitro antibacterial activity minimum inhibitory concentration (MIC) against S. aureus and E. coli at 50µg/ml than standard drug quercetin. The minimum inhibitory concentration (MIC) determination revealed that the molecules were more active against Gram positive bacteria than Gram negative bacteria. The compounds demonstrated promising antibacterial properties, with MICs ranging from 25 to 50µg/ml.

Synthesis of Tetracyclic Spirooxindolepyrrolidine-Engrafted Hydantoin Scaffolds: Crystallographic Analysis, Molecular Docking Studies and Evaluation of Their Antimicrobial, Anti-Inflammatory and Analgesic Activities

In a sustained search for novel potential drug candidates with multispectrum therapeutic application, a series of novel spirooxindoles was designed and synthesized via regioselective three-component reaction between isatin derivatives, 2-phenylglycine and diverse arylidene-imidazolidine-2,4-diones (Hydantoins). The suggested stereochemistry was ascertained by an X-ray diffraction study and NMR spectroscopy. The resulting tetracyclic heterocycles were screened for their in vitro and in vivo anti-inflammatory and analgesic activity and for their in vitro antimicrobial potency. In vitro antibacterial screening revealed that several derivatives exhibited remarkable growth inhibition against different targeted microorganisms. All tested compounds showed excellent activity against the Micrococccus luteus strain (93.75 µg/mL ≤ MIC ≤ 375 µg/mL) as compared to the reference drug tetracycline (MIC = 500 µg/mL). Compound 4e bearing a p-chlorophenyl group on the pyrrolidine ring exhibited the greatest antifungal potential toward Candida albicans and Candida krusei (MIC values of 23.43 µg/mL and 46.87 µg/mL, respectively) as compared to Amphotericin B (MIC = 31.25 and 62.50 µg/mL, respectively). The target compounds were also tested in vitro against the lipoxygenase-5 (LOX-5) enzyme. Compounds 4i and 4l showed significant inhibitory activity with IC50 = 1.09 mg/mL and IC50 = 1.01 mg/mL, respectively, more potent than the parent drug, diclofenac sodium (IC50 = 1.19 mg/mL). In addition, in vivo evaluation of anti-inflammatory and analgesic activity of these spirooxindoles were assessed through carrageenan-induced paw edema and acetic acid-induced writhing assays, respectively, revealing promising results. In silico molecular docking and predictive ADMET studies for the more active spirocompounds were also carried out.

Synthesis, Characterization, and Preliminary Antimicrobial Evaluation of New Schiff Bases and Mannich Bases of Isatin

Till now, isatin derivatives have received a lot of interest in organic and medicinal chemistry due to their significant biological and pharmacological activities. Schiff’s and Mannich bases of isatins are an effective group of heterocyclic derivatives that play a significant role in medicinal chemistry as antimicrobial agents. In light of these facts, new Schiff bases and Mannich bases of isatin were synthesized. The monomer Mannich bases; 3(a-e) have been synthesized by reacting isatin with different secondary amines, piperidine, morpholine, and pyrrolidine, dimethylamine, diphenylamine, separately, and formaldehyde, while the dimer (5) formed by using piperazine and formaldehyde which then react separately with Phenylhydrazine to form new Schiff bases 4(a-e), and dimer Schiff base (6) as final products. The structures of the newly synthesized compounds were identified using two spectroscopic methods; (Fourier- transform infrared) FTIR and proton nuclear magnetic resonance spectroscopy (¹H-NMR) analysis. The preliminary in vitro antibacterial and antifungal screening results of new isatin derivatives [4(a-e) and 6] reported moderate to potent antimicrobial activity, the compound 4c exhibited moderate broad-spectrum antibacterial and antifungal activities compared to other derivatives. Moreover, compounds 4c and 6 have a good inhibitory effect against B. subtilis while amoxicillin (standard drug) shows no activity. For antifungal activity compounds (4a-c and 4e) have considerable activity towards C. albicans, whereas compound 4d exhibits slight activity and 6 of no activity.

One‐Pot Multicomponent Synthesis of Novel Spiro‐(1,8)‐Naphthyridine Derivatives in PEG‐400

AbstractA one‐pot multi‐component pathway is reported to synthesize novel spiro‐(1,8)‐naphthyridine derivatives in good to excellent yields via the condensation reaction of isatin derivatives, malononitrile dimer and enamine derivatives. In polyethylene glycol‐400 at 80 °C, more than 30 novel products of spiro‐(1,8)‐naphthyridines were synthesized up to 95 % yields with only water as a by‐product. Separation of the products was performed efficiently and no additional operation was needed for purification of the products, except that, in some cases, recrystallization was done. Moreover, some new spiro‐dihydropyrimidines were efficiently synthesized when malononitrile (or methyl/ethyl‐2‐cyanomalonate) was employed instead of enamines.

Design, synthesis and molecular modeling of isatin-aminobenzoic acid hybrids as antibacterial and antibiofilm agents

Number of factors, including newly emerging infectious diseases and an increase in multi-drug resistant microbial pathogens with particular relevance for Gram-positive bacteria, make the treatment of infectious diseases in hospital-based healthcare a major challenge in the medical community. 4-Aminobenzoic acid (PABA), has demonstrated a variety of biological actions particularly, antimicrobial activity. In our study we coupled this vitamin-like molecule with different isatin derivatives. We investigated the antibacterial activity of the synthesized Schiff's bases. The compounds showed high selective activity against Gram-positive bacteria and showed weak or no activity against both Gram-negative bacteria and fungi. Compound 2a showed highest activity against S. aureus and B. subtilis (MIC 0.09 mmol/L). Additionally, these substances exhibit strong anti-B. Subtilis biofilm formation. We were able to shed insight on the binding mode of these new inhibitors using in silico docking of the compounds in the binding sites of a 3D structure of B. subtilis histidine kinase/Walk. The binding free energy of the compound 2a to the catalytic domain walk, of histidine kinase enzyme of B. subtilis bacteria, was calculated using molecular mechanics/generalized born surface area scoring. The key residues for macromolecule–ligand binding were postulated. The optimized 3D protein–ligand binding modes shed light on the B. subtilis HK/Walk–ligand interactions that afford a means to assess binding affinity to design new HK/Walk inhibitor as antibacterial agents.

One Pot Synthesis, Crystal Structure, Hirshfeld Studies, Docking Simulation and Antimicrobial Efficacy Assay of New Fused/Substituted Pyrazolinyl–Thiazolidinyl–Indolone Triheterocyclic Hybrid Scaffolds

In this present investigation, a new series of functionalized hybrid compounds containing three bioactive triheterocyclic templates, pyrazolines, thiazolidinones, and indolones are designed and synthesized via multicomponent, one-pot reaction of 3-(4-chlorophenyl)-5-[4-(propan-2-yl)phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide with various substituted isatin derivatives and chloroacetic acid in the presence of fused sodium acetate and glacial acetic acid viz ring closure mechanism followed by dehydration. The formation of new scaffolds 4–7(a–c) is evidenced by analytical and spectral studies. The single-crystal X-ray diffraction study supported the molecular structure of compound 4a as a triclinic crystal system with a P space group and Z = 2. Interestingly, the compound is crystallized with two molecules (A/B) and one water molecule in the asymmetric unit, and the crystal packing is stabilized by intra and intermolecular hydrogen bonds. To quantify the percentage of intermolecular contacts and electrostatic potential distribution in crystal packing, Hirshfeld surface analysis was performed. All the compounds were screened for their preliminary antimicrobial activity against a panel of bacterial and fungal strains. The newly synthesized compounds exhibited fairly encouraging in vitro antibacterial activity, so the validation of the potent compound was done by docking against the antibacterial target Escherichia coli FabH (PDB: 5BNS). The virtual screening is focused on ADME and drug-likeliness properties to identify their putative ligand-protein interactions using Schrödinger software.

Design and Synthesis of Novel 5-((3-(Trifluoromethyl)piperidin-1-yl)sulfonyl)indoline-2,3-dione Derivatives as Promising Antiviral Agents: In Vitro, In Silico, and Structure-Activity Relationship Studies.

Herein, a series of new isatin derivatives was designed and synthesized (1-9) as broad-spectrum antiviral agents. Consequently, the antiviral activities of the synthesized compounds (1-9) were pursued against three viruses, namely influenza virus (H1N1), herpes simplex virus 1 (HSV-1), and coxsackievirus B3 (COX-B3). In particular, compounds 9, 5, and 4 displayed the highest antiviral activity against H1N1, HSV-1, and COX-B3 with IC50 values of 0.0027, 0.0022, and 0.0092 µM, respectively. Compound 7 was the safest, with a CC50 value of 315,578.68 µM. Moreover, a quantitative PCR (real-time PCR) assay was carried out for the most relevant compounds. The selected compounds exhibited a decrease in viral gene expression. Additionally, the conducted in silico studies emphasized the binding affinities of the synthesized compounds and their reliable pharmacokinetic properties as well. Finally, a structure-antiviral activity relationship study was conducted to anticipate the antiviral activity change upon future structural modification.

In silico Molecular Docking Study of Isatin and Acetophenone Derivatives as Antimicrobial Agent

The heterocyclic molecule isatin (1H-indole-2,3-dione) and its derivatives form a significant family of chemicals that can be employed as building blocks for the manufacture of pharmaceuticals. In the computational method known as docking, different software tools produce different positions at which ligands attach to their receptors. With the help of the Molegro virtual docker software (Version 6.0) and the PDB 3ACX, the present study attempts to perform a high-throughput in silico screening of 27 developed isatin and acetophenone-based derivatives. The docking results showed mol dock scores of -103.345 and one hydrogen bond interaction for the standard drug Ampicillin, on the other hand, the isatin and acetophenone-based derivatives YDA 27, YDA 26, YDA 25, YDA 17 and YDA 7 exhibited excellent mol dock scores and docking scores ranging from -104.23 to -121.126. Apart from the mol dock score, most of the studied compounds observed excellent hydrogen bonding with amino acids of PDB. Compound YDA 27, YDA 26, YDA 25, YDA 17 and YDA 7 showed 3 to 7 hydrogen bond interactions, however, the standard drug Ampicillin showed H-bond interaction with 1 amino acid Val 133 and Val 137. The results of the present study confirmed the significant antimicrobial potential of some designed isatin and acetophenone-based derivatives based on their mol dock values and other parameters when studied in silico, and the data obtained will give data that supports and provides perspectives in future research to develop an effective antimicrobial agent from these derivatives.

Design and synthesis of isatin derivatives as effective SARS-CoV-2 3CL protease inhibitors.

SARS-CoV-2 chymotrypsin-like cysteine protease (3CLpro ) is one of the most widely developed drug targets for COVID-19. This study aimed to design and synthesize isatin derivatives to target SARS-CoV-2 3CLpro in a covalent binding manner. Through the process, a potent 3CLpro inhibitor (5g) was discovered with an IC50 value of 0.43 ± 0.17 μM. To understand the binding affinity and specificity of 5g as a candidate inhibitor of SARS-CoV-2 3CLpro , several assays were conducted, including FRET enzyme activity assays, thermodynamic-based and kinetic-based validation of inhibitor-target interactions, and cell-based FlipGFP assays. The interaction mechanism between 3CLpro -5g was characterized by docking. Overall, these findings suggest that 5g is a new potent SARS-CoV-2 3CLpro inhibitor for the treatment of COVID-19.

Identification of sulphonamide-tethered N-((triazol-4-yl)methyl)isatin derivatives as inhibitors of SARS-CoV-2 main protease

SARS-CoV-2 pandemic in the end of 2019 led to profound consequences on global health and economy. Till producing successful vaccination strategies, the healthcare sectors suffered from the lack of effective therapeutic agents that could control the spread of infection. Thus, academia and the pharmaceutical sector prioritise SARS-CoV-2 antiviral drug discovery. Here, we exploited previous reports highlighting the anti-SARS-CoV-2 activities of isatin-based molecules to develop novel triazolo-isatins for inhibiting main protease (Mpro) of the virus, a crucial enzyme for its replication in the host cells. Particularly, sulphonamide 6b showed promising inhibitory activity with an IC50= 0.249 µM. Additionally, 6b inhibited viral cell proliferation with an IC50 of 4.33 µg/ml, and was non-toxic to VERO-E6 cells (CC50 = 564.74 µg/ml) displaying a selectivity index of 130.4. In silico analysis of 6b disclosed its ability to interact with key residues in the enzyme active site, supporting the obtained in vitro findings.