Aldehyde dehydrogenases (ALDHs) are a family of enzymes that aid in detoxification and are overexpressed in several different malignancies. There is a correlation between increased expression of ALDH and a poor prognosis, stemness, and resistance to several drugs. Several ALDH inhibitors have been generated due to the crucial role that ALDH plays in cancer stem cells. All of these inhibitors, however, are either ineffective, very toxic, or have yet to be subjected to rigorous testing on their effectiveness. Although various drug-like compounds targeting ALDH have been reported in the literature, none have made it to routine use in the oncology clinic. As a result, new potent, non-toxic, bioavailable, and therapeutically effective ALDH inhibitors are still needed. In this study, we designed and synthesized potent multi-ALDH isoform inhibitors based on the isatin and indazole pharmacophore. Molecular docking studies and enzymatic tests revealed that among all of the synthesized analogs, compound 3 is the most potent inhibitor of ALDH1A1, ALDH3A1, and ALDH1A3, exhibiting 51.32%, 51.87%, and 36.65% inhibition, respectively. The ALDEFLUOR assay further revealed that compound 3 acts as an ALDH broad spectrum inhibitor at 500 nM. Compound 3 was also the most cytotoxic to cancer cells, with an IC50 in the range of 2.1 to 3.8 µM for ovarian, colon, and pancreatic cancer cells, compared to normal and embryonic kidney cells (IC50 7.1 to 8.7 µM). Mechanistically, compound 3 increased ROS activity due to potent multi-ALDH isoform inhibition, which increased apoptosis. Taken together, this study identified a potent multi-isoform ALDH inhibitor that could be further developed as a cancer therapeutic.

In the present work, a new class of thiazole-isatin-1,2,3-triazole hybrids (5a-5p) and precursor alkyne hybrids (6a-6d) has been reported with their in-silico studies. After structural identifications using different spectroscopic technique such as FTIR, 1H and 13C NMR and HRMS, the synthesized hybrids were explored for their biological potential using molecular docking and molecular dynamics calculations. Molecular docking results revealed that compound 5j showed maximum binding energy i.e. -10.3 and -12.6 kcal/mol against antibacterial and antifungal enzymes; 1KZN (E. coli) and 5TZ1 (C. albicans), respectively.Top of FormBottom of Form Molecular dynamics simulations for the best molecule (100 ns) followed by PBSA calculations  suggested a stable complex of 5j with 5TZ1 with binding energy of -118.760 kJ/mol as compared to 1KZN (-94.593 kJ/mol). The mean RMSD values for the 1KZN with 5j complex remained approximately 0.175 nm throughout all the time span of 100 ns in the production stages and is in the acceptable range.  Whereas, 5TZ1 with 5j complex, RMSD values exhibited variability within the range of 0.15 to 0.25 nm.

The reaction mechanism of tthe formation of azomethine ylides from isatins and sarcosine is addressed in the literature in a general manner. This computational study aims to explore the mechanistic steps for this reaction in detail and to assess the reactivity of formed ylide in a 1,3-dipolar cycloaddition reaction with 7-oxabenzonorbornadiene. For this purpose, density functional theory (DFT) calculations at the M06-2X(SMD,EtOH)/6-31G(d,p) level were employed. The results indicate that CO2 elimination is the rate-determining step, the activation barrier for 1,3-dipolar cycloaddition is lower, and the formed ylide will readily react with dipolarophiles. The substitution of isatine with electron-withdrawal groups slightly decreases the activation barrier for ylide formation.

Fluorescent cytotoxic compounds with readout delivery are crucial in chemotherapy. The growing demands of these treatment strategies require the novel heterocyclic molecules with better selectivity alongside fluorescence marker potential. In this context, a series of nine isatin Schiff base derivatives 4a-i were synthesized, characterized and evaluated for UV-visible, fluorescence, thermal and bioanalysis in order to explore the effect of structure on their bioprofiles. The analogue 4d exhibited maximum cytotoxic activity on Hella cells with percentage inhibition of 83% at 50 µM and 100% at 150 µM concentrations while 4c showed minimum cytotoxic activity with the value of 19% at 50 µM and 22% at 150 µM concentrations. Meanwhile, 4g was found to exhibit maximum inhibition potential towards Vero Cells with the percentage inhibition values of 83 at 50 µM concentration. The overall SAR study showed that the para-fluoro-substituted isatin moieties exhibited the appreciable percentage inhibition while the least activity was delivered by the isatin derivatives with para-bromo substitution.

An efficient and anions fluorescence \"on-off\" sensor of 1-(prop-2-yn-1-yl)-3-(quinolin-3-ylimino)indolin-2-one (PQI) has been developed for the selective sensing of dual anions of F- and NO3- ions in aqueous medium. Active hydrogen and Lewis acidic binding sites free, Z- isomer of isatin based π-conjugated quinoline exhibited excellent sensing activity against F- and NO3- ions in UV light. The fluorescence turns on the process accomplished via the PET \"on-off\" mechanism. The interaction between probe molecule and anions is thought to be a non-covalent interaction of the low electron density covalently bonded N-methylene moiety of propargyl isatin (-N-CH2-) of probe molecule with F- ion and the terminal acidic proton of propargyl group of isatin (-C≡C-H) with NO3- ions. The modes of anions binding with PQI and plausible mechanisms are proposed by 1H and 13C NMR titrations. The selectivity of anions sensing may be offered by the bucked structure of the Z-isomer. The calculated association constant values for PQI and F- and NO3- are ions 2.5 × 104 M-1 and 2.2 × 103 M-1, respectively, indicating strong binding interaction between the PQI and anions. The association nature of anions and probes was analyzed by a Jobs plot and the finding indicates both F- and NO3- ions are in 1:1 complexation with PQI. The limit of detection (LOD) of the probe with F- and NO3- ions is calculated and is to be 6.91 × 10-7 M and 9.93 × 10-7 M, respectively. The proposed PQI fluorophore possesses a low limit of detection (LOD) for both F- and NO3- ions which is within the WHO prescribed detection limit.

Considering early-stage drug discovery programs, the Ugi four-component reaction is a valuable, flexible, and pivotal tool, facilitating the creation of two new amide bonds in a one-pot fashion to effectively yield the desired α-aminoacylamides. Here, we highlight the reputation of this reaction approach to access number and scaffold diversity of a library of isatin-based α-acetamide carboxamide oxindole hybrids, promising anticancer agents, in a mild and fast sustainable reaction process. The library was tested against six human solid tumor cell lines, among them, non-small cell lung carcinoma, cervical adenocarcinoma, breast cancer and colon adenocarcinoma. The most potent compounds 8d, 8h and 8k showed GI50 values in the range of 1-10 μM.

The isatin group is widespread in nature and is considered to be a privileged building block for drug discovery. In order to develop novel SHP1 inhibitors with fluorescent properties as tools for SHP1 biology research, this work designed and synthesized a series of isatin derivatives. The presentive compound 5a showed good inhibitory activity against SHP1PTP with IC50 of 11 ± 3 μM, displayed about 92% inhibitory rate against MV-4-11 cell proliferation at the concentration of 20 μM, exhibited suitable fluorescent properties with a long emission wavelength and a large Stokes shift, and presented blue fluorescent imaging in HeLa cells with low cytotoxicity. This study could offer chemical tool to further understand SHP1 biology and develop novel SHP1 inhibitors in therapy.

A comprehensive review presents an illuminating exploration of the vast potential of isatin, an easily accessible organic compound. This review is a valuable resource, offering a concise yet comprehensive account of the recent breakthroughs in isatin applications in medicinal chemistry, fluorescence sensing, and organic synthesis. Moreover, it dives into the exciting advancements in isatin-based chemosensors, demonstrating their remarkable ability to detect and recognize diverse cations and anions with exceptional precision. Researchers and scientists in the fields of sensing and organic chemistry will find this review indispensable for sparking innovation and developing cutting-edge technologies with significant real-world impact.

A new series of isatin-Schiff base linked 1,2,3-triazole hybrids has been synthesized using CuAAC approach from (E)-3-(phenylimino)-1-(prop-2-yn-1-yl)indolin-2-one derivatives in high yield (73-91 %). These synthesized derivatives were characterized using FT-IR, 1H NMR, 13C NMR, 2D-NMR and HRMS spectral techniques. The in vitro antimicrobial activity assay demonstrated that most of the tested hybrids exhibited promising activity. Compound 5 j displayed significant antibacterial efficacy against P. aeruginosa and B. subtilis with MIC value of 0.0062 μmol/mL. While, 5 j also showed better antifungal potency against A. niger with MIC value of 0.0123 μmol/mL. The docking studies of most promising compounds were performed with the well-known antibacterial and antifungal targets i. e. 1KZ1, 5TZ1. Molecular modelling investigations demonstrated that hybrids 5 h and 5 l exhibited good interactions with 1KZN and 5TZ1, with binding energies of -9.6 and -11.0 kcal/mol, respectively. Further, molecular dynamics studies of the compounds showing promising binding interactions were also carried out to study the stability of complexes of these hybrids with both the targets.

Selective metal ions\' extraction and recovery has various applications in the analytical field. Metal ions need to be extracted, detected, and quantified. For that purpose, ion-imprinted polymers have earned a great deal of attention during the past two decades. Pd2+ ion-imprinted hollow silica particles including an isatin Schiff base were prepared by Schiff base condensation of (3-aminopropyl)triethoxysilane and isatin. The prepared Schiff base ligand was coordinated to the target Pd2+ cations, the polymerizable Pd-complex was set aside to form gel in the company of tetraethoxysilane and the target Pd2+ cations were subsequently removed from the cross-linked silica network by means of acidified thiourea solution. All materials throughout this synthesis process were investigated utilizing mass spectrometry, elemental analysis, FTIR, and 1H-NMR. The morphological structure of both Pd2+ ion-imprinted and non-ion-imprinted silica polymer were pictured by scanning electron microscopy. Several batches were studied exploiting both Pd2+ ion-imprinted and non-ion-imprinted silica polymer to test their functionality for selective extraction of Pd2+ cations in multi-ionic solution of Ni2+, Co2+, Cu2+, Mn2+, and Pd2+.