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1.
J Phys Chem B ; 128(25): 6123-6133, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38875519

ABSTRACT

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.


Subject(s)
Cell Proliferation , Isatin , Isatin/chemistry , Isatin/pharmacology , Isatin/chemical synthesis , Humans , HeLa Cells , Cell Proliferation/drug effects , Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 6/antagonists & inhibitors , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Structure-Activity Relationship , Molecular Structure , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/pharmacology , Cell Line, Tumor , Fluorescence
2.
Luminescence ; 39(6): e4756, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38838075

ABSTRACT

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.


Subject(s)
Isatin , Isatin/chemistry , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Molecular Structure
3.
Int J Mol Sci ; 25(12)2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38928235

ABSTRACT

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.


Subject(s)
Azo Compounds , Cycloaddition Reaction , Sarcosine , Thiosemicarbazones , Thiosemicarbazones/chemistry , Azo Compounds/chemistry , Sarcosine/chemistry , Sarcosine/analogs & derivatives , Isatin/chemistry , Models, Molecular , Density Functional Theory , Norbornanes/chemistry , Molecular Structure
4.
Bioorg Chem ; 147: 107355, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38657528

ABSTRACT

Multi target directed ligands (MTDLs) are one of the promising tools for treatment of complex disease like Alzheimer's disease (AD). In this study, using rational design, we synthesized new 15 hybrids of the s-triazine, isatin and aniline derivatives as anti- AD compounds. The design was as way as that new compounds could had anti cholinesterase (ChE), antioxidant and biometal chelation ability. In vitro biological evaluation against ChE enzymes showed that these molecules were excellent inhibitors with IC50 values ranging from 0.2 nM to 734.5 nM for acetylcholinesterase (AChE), and 0.02 µM to 1.92 µM for butyrylcholinesterase (BChE). Among these compounds, 8 l with IC50 AChE = 0.7 nM, IC50 BChE = 0.09 µM and 8n with IC50 AChE = 0.2 nM, IC50 BChE = 0.03 µM were the most potent compounds. In silico studies showed that these molecules had key and effective interactions with the corresponding enzymes residues. The molecules with hydroxyl group on aniline moiety had also good antioxidant activity with EC50 values ranging from 64.2 µM to 103.6 µM. The UV-Vis spectroscopy study revealed that molecule 8n was also able to chelate biometals such as Zn2+, Cu2+and Fe2+ properly. It was concluded that these molecules could be excellent lead compounds for future studies.


Subject(s)
Acetylcholinesterase , Alzheimer Disease , Aniline Compounds , Butyrylcholinesterase , Cholinesterase Inhibitors , Drug Design , Isatin , Triazines , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Aniline Compounds/chemistry , Aniline Compounds/pharmacology , Aniline Compounds/chemical synthesis , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/chemical synthesis , Butyrylcholinesterase/metabolism , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/chemical synthesis , Dose-Response Relationship, Drug , Isatin/chemistry , Isatin/pharmacology , Isatin/chemical synthesis , Molecular Docking Simulation , Molecular Structure , Structure-Activity Relationship , Triazines/chemistry , Triazines/pharmacology , Triazines/chemical synthesis
5.
Arch Pharm (Weinheim) ; 357(6): e2300718, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38466120

ABSTRACT

A new series of isatin-linked benzenesulfonamide derivatives (9a-w) were synthesized using the tail approach and assayed for their inhibitory potency against four different human carbonic anhydrase (hCA) isoforms, hCA I, II, IX, and XII. Most of these synthesized compounds exhibited interesting inhibition potency against isoforms hCA I, IX, and XII in the nanomolar range and by taking the standard drug acetazolamide. The most potent compounds in the case of hCA I were 9c (435.8 nM) and 9s (956.4 nM), for hCA IX, 9a (60.5 nM), 9d (95.6 nM), 9g (92.1 nM), and 9k (75.4 nM), and for hCA XII, 9p (84.5 nM). However, these compounds showed more selectivity toward hCA IX over hCA I, II, and XII. Thus, these compounds can be further developed as potential lead molecules for the development of isoform-selective hCA IX inhibitors with further structural modifications.


Subject(s)
Benzenesulfonamides , Carbonic Anhydrase Inhibitors , Carbonic Anhydrases , Drug Design , Sulfonamides , Carbonic Anhydrase Inhibitors/pharmacology , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Humans , Structure-Activity Relationship , Sulfonamides/pharmacology , Sulfonamides/chemical synthesis , Sulfonamides/chemistry , Carbonic Anhydrases/metabolism , Molecular Structure , Isoenzymes/antagonists & inhibitors , Isoenzymes/metabolism , Isatin/pharmacology , Isatin/chemistry , Isatin/chemical synthesis , Dose-Response Relationship, Drug
6.
Chem Biol Interact ; 394: 110954, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38518852

ABSTRACT

The literature reports that thiazole and isatin nuclei present a range of biological activities, with an emphasis on anticancer activity. Therefore, our proposal was to make a series of compounds using the molecular hybridization strategy, which has been used by our research group, producing hybrid molecules containing the thiazole and isatin nuclei. After structural planning and synthesis, the compounds were characterized and evaluated in vitro against breast cancer cell lines (T-47D, MCF-7 and MDA-MB-231) and against normal cells (PBMC). The activity profile on membrane proteins involved in chemoresistance and tumorigenic signaling proteins was also evaluated. Among the compounds tested, the compounds 4c and 4a stood out with IC50 values of 1.23 and 1.39 µM, respectively, against the MDA-MB-231 cell line. Both compounds exhibited IC50 values of 0.45 µM for the MCF-7 cell line. Compounds 4a and 4c significantly decreased P-gp mRNA expression levels in MCF-7, 4 and 2 folds respectively. Regarding the impact on tumorigenic signaling proteins, compound 4a inhibited Akt2 in MDA-MB-231 and compound 4c inhibited the mRNA expression of VIM in MCF-7.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Isatin , Proto-Oncogene Proteins c-akt , RNA, Messenger , Thiazoles , Humans , Proto-Oncogene Proteins c-akt/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Isatin/pharmacology , Isatin/chemistry , Isatin/chemical synthesis , Cell Line, Tumor , RNA, Messenger/metabolism , RNA, Messenger/genetics , Thiazoles/pharmacology , Thiazoles/chemistry , Female , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Molecular Docking Simulation , MCF-7 Cells , Drug Screening Assays, Antitumor , Structure-Activity Relationship
7.
BMC Genomics ; 25(1): 162, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38331729

ABSTRACT

In this work, a novel isatin-Schiff base L2 had been synthesized through a simple reaction between isatin and 2-amino-5-methylthio-1,3,4-thiadiazole. The produced Schiff base L2 was then subjected to a hydrothermal reaction with cerium chloride to produce the cerium (III)-Schiff base complex C2. Several spectroscopic methods, including mass spectra, FT-IR, elemental analysis, UV-vis, 13C-NMR, 1H-NMR, Thermogravimetric Analysis, HR-TEM, and FE-SEM/EDX, were used to completely characterize the produced L2 and C2. A computer simulation was performed using the MOE software program to find out the probable biological resistance of studied compounds against the proteins in some types of bacteria or fungi. To investigate the interaction between the ligand and its complex, we conducted molecular docking simulations using the molecular operating environment (MOE). The docking simulation findings revealed that the complex displayed greater efficacy and demonstrated a stronger affinity for Avr2 effector protein from the fungal plant pathogen Fusarium oxysporum (code 5OD4) than the original ligand. The antibacterial activity of the ligand and its Ce3+ complex were applied in vitro tests against different microorganism. The study showed that the complex was found to be more effective than the ligand.


Subject(s)
Cerium , Isatin , Molecular Docking Simulation , Spectroscopy, Fourier Transform Infrared , Isatin/pharmacology , Isatin/chemistry , Cerium/pharmacology , Schiff Bases/pharmacology , Schiff Bases/chemistry , Computer Simulation , Ligands , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests
8.
Chem Biodivers ; 21(4): e202301612, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38332679

ABSTRACT

Heterocyclic compounds containing 1,2,3-triazole and isatin as core structures have emerged as promising drug candidates due to their diverse biological activities such as anti-cancer, antifungal, antimicrobial, antitumor, anti-epileptic, antiviral, and more. The presence of 1,2,3-triazoles and isatin heterocycles in these hybrids, both individually known for their medicinal significance, has increasingly piqued the interest of drug discovery researchers, as they seek to delve deeper into their extensive pharmacological potential for enhancing therapeutic efficacy. Moreover, these hybrid compounds are synthetically accessible using readily available materials. Therefore, there is a pressing need to provide a comprehensive overview of the existing knowledge in this field, offering valuable insights to readers and paving the way for the discovery of novel 1,2,3-triazole-linked isatin hybrids with therapeutic potential.


Subject(s)
Anti-Infective Agents , Isatin , Neoplasms , Humans , Triazoles/pharmacology , Triazoles/chemistry , Structure-Activity Relationship , Isatin/pharmacology , Isatin/chemistry , Anti-Infective Agents/pharmacology
9.
Chem Biodivers ; 21(6): e202301942, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38393713

ABSTRACT

This article reports one-pot synthesis of ten novel spirooxindoles using 5-methyl-2-thiohydantoin, isatin derivatives, and malononitrile in good to high yields (65-90 %). The structures of the synthesized compounds were deduced by 1H-NMR, 13C NMR, FT-IR, and Mass spectral data. The antibacterial activity of the compounds was evaluated against two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) based on the Kirby-Bauer method. According to the obtained data, the synthesized compounds show more activity against Gram-positive bacteria than Gram-negative bacteria. Also, the antioxidant activity of these compounds was measured using the DPPH radical scavenging test method, which showed good to excellent activity (59.65-94.03 %). Among them, the chlorinated derivatives (4 f-j) exhibited more antioxidant activity (84.85-94.03 %) than the other compounds (4 a-e) (56.65-74.4 %) and even ascorbic acid as a standard antioxidant compound (82.3 %).


Subject(s)
Anti-Bacterial Agents , Antioxidants , Indoles , Microbial Sensitivity Tests , Spiro Compounds , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antioxidants/pharmacology , Antioxidants/chemical synthesis , Antioxidants/chemistry , Biphenyl Compounds/antagonists & inhibitors , Biphenyl Compounds/chemistry , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Indoles/chemistry , Indoles/pharmacology , Indoles/chemical synthesis , Molecular Structure , Oxindoles/pharmacology , Oxindoles/chemistry , Oxindoles/chemical synthesis , Picrates/antagonists & inhibitors , Pseudomonas aeruginosa/drug effects , Spiro Compounds/chemistry , Spiro Compounds/pharmacology , Spiro Compounds/chemical synthesis , Spirooxindoles , Staphylococcus aureus/drug effects , Structure-Activity Relationship , Isatin/chemical synthesis , Isatin/chemistry , Isatin/pharmacology
10.
Bioorg Med Chem ; 98: 117586, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38171252

ABSTRACT

Breast cancer causes a high rate of mortality all over the world. Therefore, the present study focuses on the anticancer activity of new lower rim-functionalized calix[4]arenes integrated with isatin and the p-position of calixarenes with 1,4-dimethylpyridinium iodine against various human cancer cells such as MCF-7 and MDA-MB-231 breast cancer cell lines, as well as the PNT1A healthy epithelial cell line. It was observed that compound 6c had the lowest values in MCF-7 (8.83 µM) and MDA-MB-231 (3.32 µM). Cell imaging and apoptotic activity studies were performed using confocal microscopy and flow cytometry, respectively. The confocal imaging studies with 6c showed that the compound easily entered the cell, and it was observed that 6c accumulated in the mitochondria. The Comet assay test was used to detect DNA damage of compounds in cells. It was found that treated cells had abnormal tail nuclei and damaged DNA structures compared with untreated cells. In vitro human aromatase enzyme inhibition profiles showed that compound 6c had a remarkable inhibitory effect on aromatase. Compound 6c displayed a significant inhibition capacity on aromatase enzyme with the IC50 value of 0.104 ± 0.004 µM. Thus, not only the anticancer activity of the new fluorescent derivatives, which are the subject of this study, but the aromatase inhibitory profiles have also been proven.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Isatin , Humans , Female , Aromatase Inhibitors/pharmacology , Antineoplastic Agents/chemistry , Isatin/pharmacology , Isatin/chemistry , Aromatase/metabolism , Structure-Activity Relationship , Cell Line, Tumor , Mitochondria , DNA , Cell Proliferation , Drug Screening Assays, Antitumor
11.
Bioorg Med Chem Lett ; 99: 129613, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38224754

ABSTRACT

A series of bis-isatin conjugates with lysine linker were synthesized with the aim of probing their antiproliferative potential. All the newly synthesized derivatives (0-100 µM) were first screened against liver cancer cell lines(Huh1, H22, Huh7, Hepa1-6, HepG2, Huh6 and 97H) using CCK-8 assay. Results indicated that the derivative 4d exhibited the most potent activity against Huh1 (IC50 = 17.13 µM) and Huh7(IC50 = 8.265 µM). In vivo anti-tumor study showed that compound 4d effectively inhibited tumor growth in Huh1-induced xenograft mouse model; the anti-tumor effect of compound 4d (15 mg/kg) was comparable with sorafenib (20 mg/kg). H&E staining analysis and routine blood test and blood serum biochemistry examination was performed to confirm the safety of compound 4d in xenograft models. The mechanism of action of 4d on tumor growth inhibition was further investigated by RNA-Seq analysis, which indicates a positive regulation of autophagy signaling pathway, which was further confirmed with key biomarker expression of autophagy after 4d treatment. Our results suggest that the bis-isatin conjugate compound 4d is a promising tumor inhibitory agent for some liver cancer.


Subject(s)
Antineoplastic Agents , Isatin , Liver Neoplasms , Humans , Animals , Mice , Cell Line, Tumor , Isatin/chemistry , Drug Screening Assays, Antitumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Liver Neoplasms/drug therapy , Cell Proliferation , Structure-Activity Relationship , Molecular Structure
12.
Nat Commun ; 15(1): 859, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38286847

ABSTRACT

Proteins labelled site-specifically with small molecules are valuable assets for chemical biology and drug development. The unique reactivity profile of the 1,2-aminothiol moiety of N-terminal cysteines (N-Cys) of proteins renders it highly attractive for regioselective protein labelling. Herein, we report an ultrafast Z-selective reaction between isatin-derived Baylis Hillman adducts and 1,2-aminothiols to form a bis-heterocyclic scaffold, and employ it for stable protein bioconjugation under both in vitro and live-cell conditions. We refer to our protein bioconjugation technology as Baylis Hillman orchestrated protein aminothiol labelling (BHoPAL). Furthermore, we report a lipoic acid ligase-based technology for introducing the 1,2-aminothiol moiety at any desired site within proteins, rendering BHoPAL location-agnostic (not limited to N-Cys). By using this approach in tandem with BHoPAL, we generate dually labelled protein bioconjugates appended with different labels at two distinct specific sites on a single protein molecule. Taken together, the protein bioconjugation toolkit that we disclose herein will contribute towards the generation of both mono and multi-labelled protein-small molecule bioconjugates for applications as diverse as biophysical assays, cellular imaging, and the production of therapeutic protein-drug conjugates. In addition to protein bioconjugation, the bis-heterocyclic scaffold we report herein will find applications in synthetic and medicinal chemistry.


Subject(s)
Isatin , Molecular Structure , Isatin/chemistry , Sulfhydryl Compounds , Cysteine
13.
J Enzyme Inhib Med Chem ; 38(1): 2203389, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37122176

ABSTRACT

In this work, new isatin-based sulphonamides (6a-i, 11a-c, 12a-c) were designed and synthesised as potential dual VEGFR-2 and carbonic anhydrase inhibitors with anticancer activities. Firstly, all target isatins were examined for in vitro antitumor action on NCI-USA panel (58 tumour cell lines). Then, the most potent derivatives were examined for the potential CA inhibitory action towards the physiologically relevant hCA isoforms I, II, and tumour-linked hCA IX isoform, in addition, the VEGFR-2 inhibitory activity was evaluated. The target sulphonamides failed to inhibit the CA isoforms that could be attributable to the steric effect of the neighbouring methoxy group, whereas they displayed potent VEGFR-2 inhibitory effect. Following that, isatins 11b and 12b were tested for their influence on the cell cycle disturbance, and towards the apoptotic potential. Finally, detailed molecular modelling analyses, including docking and molecular dynamics, were carried out to assess the binding mode and stability of target isatins.


Subject(s)
Antineoplastic Agents , Carbonic Anhydrases , Isatin , Molecular Structure , Structure-Activity Relationship , Carbonic Anhydrases/metabolism , Isatin/pharmacology , Isatin/chemistry , Vascular Endothelial Growth Factor Receptor-2 , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Sulfonamides/pharmacology , Sulfonamides/chemistry , Carbonic Anhydrase Inhibitors/pharmacology , Carbonic Anhydrase Inhibitors/chemistry , Carbonic Anhydrase IX , Antigens, Neoplasm/metabolism
14.
Medicina (Kaunas) ; 59(3)2023 Mar 19.
Article in English | MEDLINE | ID: mdl-36984611

ABSTRACT

The traditional single-treatment strategy for cancer is frequently unsuccessful due to the complexity of cellular signaling. However, suppression of multiple targets is vital to defeat tumor cells. In this research, new compounds for the treatment of cancer were developed successfully as novel hybrid anticancer agents. Based on a molecular hybridization strategy, we designed hybrid agents that target multiple protein kinases to fight cancer cells. The proposed hybrid agents combined purine and isatin moieties in their structures with 4-aminobenzohydrazide and hydrazine as different linkers. Having those two moieties in one molecule enabled the capability to inhibit multiple kinases, such as human epidermal receptor (EGFR), human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor 2 (VEGFR2) and cyclin-dependent kinase 2 (CDK2). Anticancer activity was evaluated by performing cytotoxicity assays, kinase inhibition assays, cell cycle analysis, and BAX, Bcl-2, Caspase 3 and Caspase 9 protein level determination assays. The results showed that the designed hybrids tackled the cancer by inhibiting both cell proliferation and metastasis. A molecular docking study was performed to predict possible binding interactions in the active site of the investigated protein kinase enzymes.


Subject(s)
Antineoplastic Agents , Isatin , Neoplasms , Humans , Isatin/pharmacology , Isatin/chemistry , Isatin/therapeutic use , Molecular Docking Simulation , Vascular Endothelial Growth Factor A , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Neoplasms/drug therapy , Cell Proliferation , Apoptosis , Purines/pharmacology , Purines/therapeutic use , Cell Line, Tumor
15.
Curr Top Med Chem ; 23(10): 833-847, 2023.
Article in English | MEDLINE | ID: mdl-36733194

ABSTRACT

Molecular hybridization is one of the recent stratagems in medicinal chemistry to synthesize a novel hybrid molecule having better affinity and efficacy by combining two or more pharmacophoric moieties. Molecular hybridization, i.e., a linker or framework integration technique, can be used to connect the two pharmacophoric components. It has often been found that hybrid compounds perform more effectively and possess lower toxicity than their parent molecules. In order to create a new generation of effective and safe therapeutic candidates, such as anti-cancer, anti-viral, anti-HIV, antioxidant, and antibacterial, for a variety of frontline diseases, several articles have been published that discuss the molecular hybridization of preclinically or clinically proven compounds. Isatin and its derivatives have been studied extensively due to diversified biological activities, including antitumor, antimicrobial, anti-inflammatory, analgesic, antiviral, antioxidant, anticonvulsant, etc. Similarly, 1,2,3-triazoles have received significant interest as a bio-isostere in medicinal chemistry for generating a large number of pharmaceutically significant molecules. As it possesses diversified physiochemical properties, such as hydrogen bond formation capacity, ease of synthesis, moderate dipole moment, stability towards acidic/basic hydrolysis, inertness towards oxidizing/ reducing agents, and good binding potential with several biological targets, triazole is an important choice of the medicinal chemists for the novel medication development. The aim of the current review is to summarize the research articles showing the pharmacological significance of hybrid molecules containing isatin and 1,2,3-triazole moieties. The present review may assist chemists in designing and synthesizing isatin-1,2,3-triazole hybrids with better efficacy and low cytotoxicity.


Subject(s)
Isatin , Triazoles , Triazoles/pharmacology , Triazoles/chemistry , Structure-Activity Relationship , Isatin/pharmacology , Isatin/chemistry , Antioxidants/pharmacology , Anti-Bacterial Agents/pharmacology , Antiviral Agents/pharmacology
16.
Bioorg Chem ; 133: 106388, 2023 04.
Article in English | MEDLINE | ID: mdl-36736034

ABSTRACT

In present era, heterocyclic compounds containing two or three nitrogen atoms play a vital role in drug discovery. In this context, a new class of isatin-semicarbazone tethered 1,2,3-triazole hybrids was synthesized via Cu(I)-mediated azide alkyne cycloaddition reaction. Structural characteristics of the newly derived compounds were identified by various spectral techniques like FTIR, 1H NMR, 13C NMR, HRMS and single crystal X-ray crystallography. Synthesized derivatives were also screened for in vitro antimicrobial and antibiofilm activity against different microbial species. Triazole hybrid 7e showed significant efficacy towards E. coli having MIC of 0.0063 µmol/mL, whereas 6a, 6b, 7a, 7c, 7e, and 7f showed highest percentage of biofilm inhibition against P. aeruginosa. Bioassay results suggested that these triazole hybrids could act as biomaterial for antimicrobial and antibiofilm applications and may constitute a new promising class of antimicrobial and antibiofilm agents. These results were further supported by in silico docking, DFT calculations and ADME studies.


Subject(s)
Anti-Infective Agents , Isatin , Semicarbazones , Structure-Activity Relationship , Isatin/pharmacology , Isatin/chemistry , Semicarbazones/pharmacology , Triazoles/pharmacology , Triazoles/chemistry , Escherichia coli , Anti-Infective Agents/pharmacology , Microbial Sensitivity Tests , Molecular Structure , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
17.
Int J Mol Sci ; 24(4)2023 Feb 13.
Article in English | MEDLINE | ID: mdl-36835183

ABSTRACT

N-fused pyrrolidinyl spirooxindole belongs to a class of privileged heterocyclic scaffolds and is prevalent in natural alkaloids and synthetic pharmaceutical molecules. To realize the switchable synthesis of divergent N-fused pyrrolidinyl spirooxindoles for further biological activity evaluation via a substrate-controlled strategy, a chemically sustainable, catalysis-free, and dipolarophile-controlled three-component 1,3-dipolar cycloaddition of isatin-derived azomethine ylides with diverse dipolarophiles is described in this work. A total of 40 functionalized N-fused pyrrolidinyl spirooxindoles were synthesized in 76-95% yields with excellent diastereoselectivities (up to >99:1 dr). The scaffolds of these products can be well-controlled by employing different 1,4-enedione derivatives as dipolarophiles in EtOH at room temperature. This study provides an efficient strategy to afford a spectrum of natural-like and potentially bioactive N-fused pyrrolidinyl spirooxindoles.


Subject(s)
Isatin , Cycloaddition Reaction , Isatin/chemistry
18.
Molecules ; 28(2)2023 Jan 07.
Article in English | MEDLINE | ID: mdl-36677676

ABSTRACT

Spirooxindoles occupy an important place in heterocyclic chemistry. Many natural spirooxindole-containing compounds have been identified as bio-promising agents. Synthetic analogs have also been synthesized utilizing different pathways. The present article summarizes the recent development of both natural and synthetic spirooxindole-containing compounds prepared from isatin or its derivatives reported in the last five years. The spirooxindoles are categorized based on their mentioned biological properties.


Subject(s)
Isatin , Spiro Compounds , Indoles/chemistry , Spiro Compounds/pharmacology , Spiro Compounds/chemistry , Isatin/pharmacology , Isatin/chemistry
19.
Macromol Rapid Commun ; 44(6): e2200826, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36414542

ABSTRACT

Polymers of intrinsic microporosity (PIMs) are a class of microporous organic materials that contain interconnected pores of less than 2 nm in diameter. Such materials are of great potential used in membranes for molecular separation, such as drug fractionation in pharmaceutical industry. However, the PIMs membranes are often susceptible to low separation selectivity toward different molecules due to their wide pore size distribution. Herein, a linear polyimide, Matrimid, is incorporated with PIM-1 (a typical member of PIMs) by solution blending, and the blends are dip-coated onto a polyimide P84 support membrane to prepare thin-film composite (TFC) membranes to control pore size distribution while keep high microporosity. The component miscibility, pore characteristics, and molecular separation performances of the Matrimid/PIM-1 TFC membranes are investigated in detail. The Matrimid and PIM-1 are partially miscible due to their similar Hansen solubility parameters. The Matrimid endows the selective layers (coatings) with narrower pore size distribution due to more compact chain packing. The prepared Matrimid/PIM-1 TFC membranes show high selectivity for separation of riboflavin (80% of retention) and isatin (only 5% of retention). The developed membranes exhibit great potential for separating molecules with different molecular weights.


Subject(s)
Chemical Fractionation , Membranes, Artificial , Polymers , Solvents , Chemical Fractionation/methods , Isatin/chemistry , Isatin/isolation & purification , Permeability , Polymers/chemistry , Porosity , Riboflavin/chemistry , Riboflavin/isolation & purification , Solubility , Solvents/chemistry
20.
Mol Divers ; 27(5): 2365-2397, 2023 Oct.
Article in English | MEDLINE | ID: mdl-35925529

ABSTRACT

The unique therapeutic and biological characteristics of spirooxindole have led to the presentation of numerous reactions for the synthesis of spirooxindoles through 1,3-Dipolar cycloaddition of highly reactive isatin-derived azomethine ylides with activated olefins as the main tool for the formation of spirocyclic oxindoles during the last 4 years. Therefore, there is a need to highlight the recent developments in this area, along with the representative synthetic methods and relevant reaction mechanisms from 2018 to 2021. The representative synthetic methodologies were listed in four sections based on the procedure to form the azomethine ylide species including isatins and amino acids, isatin-derived α-(trifluoromethyl)imine, isatins and benzylamines, and from isatin-derived cyclic imine 1,3-dipoles.


Subject(s)
Isatin , Spiro Compounds , Isatin/chemistry , Cycloaddition Reaction , Spiro Compounds/chemistry , Indoles/chemistry , Imines
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