Organocatalytic Synthesis and DNA Interactive Studies of New 1,2,3-triazolyl-thiazolidines Hybrids.

An organocatalytic [3+2] cycloaddition reaction between thiazolidine-containing ß-ketoester 1 and aryl azides 2 was employed to synthesize new 1,2,3-triazolyl-thiazolidine hybrids 3. In this metal-free approach, twelve compounds were isolated in yields ranging from 23 % to 96 % by using diethylamine (10 mol%) and DMSO at 75 °C for 24 hours. DNA-binding assays were conducted through absorption, emission spectroscopy and viscosimetry analysis, to evaluate the interaction capacity of the studied derivatives with nucleic acids. All the synthesized compounds were evaluated for their interactions with a specific group of compounds containing the pharmacophoric groups triazole and thiazolidine through a molecular docking speculative study, aimed at identifying the interaction profile of these compounds with DNA. The obtained results suggest that 1,2,3-triazolyl-thiazolidine hybrids could be a promising approach in the development of novel therapeutic agents targeting DNA-related processes.

Catching some air: a method to spatially quantify aerial triazole resistance in Aspergillus fumigatus.

Airborne triazole-resistant spores of the human fungal pathogen Aspergillus fumigatus are a significant human health problem as the agricultural use of triazoles has been selecting for cross-resistance to life-saving clinical triazoles. However, how to quantify exposure to airborne triazole-resistant spores remains unclear. Here, we describe a method for cost-effective wide-scale outdoor air sampling to measure both spore abundance as well as antifungal resistance fractions. We show that prolonged outdoor exposure of sticky seals placed in delta traps, when combined with a two-layered cultivation approach, can regionally yield sufficient colony-forming units (CFUs) for the quantitative assessment of aerial resistance levels at a spatial scale that was up to now unfeasible. When testing our method in a European pilot sampling 12 regions, we demonstrate that there are significant regional differences in airborne CFU numbers, and the triazole-resistant fraction of airborne spores is widespread and varies between 0 and 0.1 for itraconazole (∼4 mg/L) and voriconazole (∼2 mg/L). Our efficient and accessible air sampling protocol opens up extensive options for fine-scale spatial sampling and surveillance studies of airborne A. fumigatus.IMPORTANCEAspergillus fumigatus is an opportunistic fungal pathogen that humans and other animals are primarily exposed to through inhalation. Due to the limited availability of antifungals, resistance to the first choice class of antifungals, the triazoles, in A. fumigatus can make infections by this fungus untreatable and uncurable. Here, we describe and validate a method that allows for the quantification of airborne resistance fractions and quick genotyping of A. fumigatus TR-types. Our pilot study provides proof of concept of the suitability of the method for use by citizen-scientists for large-scale spatial air sampling. Spatial air sampling can open up extensive options for surveillance, health-risk assessment, and the study of landscape-level ecology of A. fumigatus, as well as investigating the environmental drivers of triazole resistance.

1,2,3-Triazole-Containing Azamacrocycles from Chiral Triazolopeptoids: Synthesis and Solid-State Studies.

Two new chiral 1,2,3-triazole-containing macrocyclic oligoamides (i. e.: triazolopeptoid 4 and 5) were obtained through solid-phase synthesis of linear precursors followed by high dilution macrocyclization reaction. Theoretical (DFT) and spectroscopic (NMR) studies revealed the intricate interplay between the Nα-chiral side chains and their conformational attitudes. BH3-mediated reduction of the tertiary amide groups of known 1-3 and newly synthesized 4 gave novel azamacrocycles 6-9. Detection of borane complexes of azamacrocycles 6 and 9 (i. e.: 10 and 11), corroborated by X-ray diffraction studies, demonstrated the peculiar properties of 1,2,3-triazole-containing macrorings.

Each Interruption is an Opportunity: Novel Synthetic Strategies Explored Through Interrupted Click Reactions.

The particular and unique mechanism of the copper-catalyzed reaction between azides and alkynes (CuAAC) has not only allowed for the efficient synthesis of 1,2,3-trisubstituted 1,4-triazoles in excellent yields and under mild conditions, becoming the quintessential click reaction, but it has also enabled the straightforward formation of a metallocycle intermediate, the copper triazolyl. This, under suitable reaction conditions able to suppress its protonolysis, can be used either for the creation of new bicyclic triazolyl structures or for the generation of novel three or four-component reactions. The aim of this review is to rationalize and unify all these transformations, which are collectively referred to as "interrupted click reactions".

Comprehensive Review on the Synthesis of [1,2,3]Triazolo[1,5-a]Quinolines.

This report outlines the evolution and recent progress about the different protocols to synthesize the N-heterocycles fused hybrids, specifically [1,2,3]triazolo[1,5-a]quinoline. This review encompasses a broad range of approaches, describing several reactions for obtaining this since, such as dehydrogenative cyclization, oxidative N-N coupling, Dieckmann condensation, intramolecular Heck, (3+2)-cycloaddition, Ullman-type coupling and direct intramolecular arylation reactions. We divided this review in three section based in the starting materials to synthesize the target [1,2,3]triazolo[1,5-a]quinolines. Starting materials containing quinoline or triazole units previously formed, as well as starting materials which both quinoline and triazole units are formed in situ. Different methods of obtaining are described, such as metal-free or catalyzed conditions, azide-free, using conventional heating or alternative energy sources, such as electrochemical and photochemical methods. Mechanistic insights underlying the reported reactions were also described in this comprehensive review.

Design, synthesis and antitubercular assessment of 1, 2, 3-triazole incorporated thiazolylcarboxylate derivatives.

A library of 1, 2, 3-triazole incorporated thiazolylcarboxylate derivatives (7a-q) and (8a-j) were synthesized and evaluated for their in-vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The two compounds 7h and 8h have displayed excellent antitubercular activity with MIC values of 3.12 and 1.56 µg/mL respectively (MIC values of standard drugs; Ciprofloxacin 1.56 µg/mL & Ethambutol 3.12 µg/mL). Whereas, the four compounds 7i, 7n, 7p and 8i displayed noticeable antitubercular activity with a MIC value of 6.25 µg/mL. The active compounds of the series were further studied for their cytotoxicity against RAW264.7 cell line using MTT assay. Furthermore, to study the probable mechanism of antitubercular action, physicochemical property profiling, DFT calculation and molecular docking study were executed on mycobacterial cell wall target Decaprenylphosphoryl-ß-d-ribose 2'-epimerase 1 (DprE1). Among all the compounds, 7h (-10 kcal/mol) and 8h (-10.1 kcal/mol) exerted the highest negative binding affinity against the targeted DprE1 (PDB: 4NCR) protein.

1,3,4,5-Tetrasubstituted Poly(1,2,3-triazolium) Obtained through Metal-Free AA+BB Polyaddition of a Diazide and an Activated Internal Dialkyne.

A tetra(ethylene glycol)-based 1,3,4,5-tetrasubstituted poly(1,2,3-triazolium) is synthesized in two steps including: i) the catalyst-free polyaddition of a diazide and an activated internal dialkyne and ii) the N-alkylation of the resulting 1,2,3-triazole groups. In order to provide detailed structure/properties correlations different analogs are also synthesized. First, parent poly(1,2,3-triazole)s are obtained via AA+BB polyaddition using copper(I)-catalyzed alkyne-azide cycloaddition or metal-free thermal alkyne-azide cycloaddition (TAAC). Poly(1,2,3-triazole)s with higher molar masses are obtained in higher yields by TAAC polyaddition. A 1,3,4-trisubstituted poly(1,2,3-triazolium) structural analog obtained by TAAC polyaddition using a terminal activated dialkyne and subsequent N-alkylation of the 1,2,3-triazole groups enables discussing the influence of the methyl group in the C-4 or C-5 position on thermal and ion conducting properties. Obtained polymers are characterized by 1H, 13C, and 19F NMR spectroscopy, differential scanning calorimetry, thermogravimetric analysis, size exclusion chromatography, and broadband dielectric spectroscopy. The targeted 1,3,4,5-tetrasubstituted poly(1,2,3-triazolium) exhibits a glass transition temperature of -23 °C and a direct current ionic conductivity of 2.0 × 10-6 S cm-1 at 30 °C under anhydrous conditions. The developed strategy offers opportunities to further tune the electron delocalization of the 1,2,3-triazolium cation and the properties of poly(1,2,3-triazolium)s using this additional substituent as structural handle.

Unveiling the anti-cancer potentiality of phthalimide-based Analogues targeting tubulin polymerization in MCF-7 cancerous Cells: Rational design, chemical Synthesis, and Biological-coupled Computational investigation.

The present study deals with an anti-cancer investigation of an array of phthalimide-1,2,3-triazole molecular conjugates with various sulfonamide fragments against human breast MCF-7 and prostate PC3 cancer cell lines. The targeted 1,2,3-triazole derivatives 4a-l and 6a-c were synthesized from focused phthalimide-based alkyne precursors using a facile click synthesis approach and were thoroughly characterized using several spectroscopic techniques (IR, 1H, 13C NMR, and elemental analysis). The hybrid click adducts 4b, 4 h, and 6c displayed cytotoxic potency (IC50 values of 1.49, 1.07, and 0.56 µM, respectively) against MCF-7 cells. On the contrary, none of the synthesized compounds showed apparent cytotoxic efficacy for PC3 cells (IC50 ranging from 9.87- >100 µM). As a part of the mechanism analysis, compound 6c demonstrated a potent inhibitory effect (78.3 % inhibition) of tubulin polymerization in vitro with an IC50 value of 6.53 µM. In addition, biological assays showed that compound 6c could prompt apoptotic cell death and induce G2/M cell cycle arrest in MCF-7 cells. Accordingly, compound 6c can be further developed as an anti-breast cancer agent through apoptosis-induction.

Design, synthesis and anti-inflammatory assessment of certain substituted 1,2,4-triazoles bearing tetrahydroisoquinoline scaffold as COX 1/2-inhibitors.

Aiming to discover effective and safe non-steroidal anti-inflammatory agents, a new set of 1,2,4-triazole tetrahydroisoquinoline hybrids 9a-g, 11a-g and 12a-g was synthesized and evaluated as inhibitors of COX-1 and COX-2. In order to overcome the adverse effects of highly selective COX-2 and non-selective COX-2 inhibitors, the compounds of this study were designed with the goal of obtaining moderately selective COX-2 inhibitors. In this study compounds 9e, 9g and 11f are the most effective derivatives against COX-2 with IC50 values 0.87, 1.27 and 0.58 µM, respectively which are better than or comparable to the standard drug celecoxib (IC50 = 0.82 µM) but with lower selectivity indices as required by our goal design. The results of the in vivo anti-inflammatory inhibition test revealed that compounds 9e, 9g and 11f displayed a higher significant anti-inflammatory activity than celecoxib at all-time intervals. In addition, these compounds significantly decreased the production of inflammatory mediators PGE-2, TNF-ɑ and IL-6. Compounds 9e, 9g and 11f had a safe gastric profile compared to indomethacin, also compound 11f (ulcerogenic index = 1.33) was less ulcerous than the safe celecoxib (ulcerogenic index = 3). Moreover, histopathological investigations revealed a normal architecture of both paw skin and gastric mucosa after oral treatment of rats with compound 11f. Furthermore, molecular docking studies were performed on COX-1 and COX-2 to study the binding pattern of compounds 9e, 9g and 11f on both isoenzymes.

An updated review on 1,2,3-/1,2,4-triazoles: synthesis and diverse range of biological potential.

The synthesis of triazoles has attracted a lot of interest in the field of organic chemistry because of its versatile chemical characteristics and possible biological uses. This review offers an extensive overview of the different pathways used in the production of triazoles. A detailed analysis of recent research indicates that triazole compounds have a potential range of pharmacological activities, including the ability to inhibit enzymes, and have antibacterial, anticancer, and antifungal activities. The integration of computational and experimental methods provides a thorough understanding of the structure-activity connection, promoting sensible drug design and optimization. By including triazoles as essential components in drug discovery, researchers can further explore and innovate in the synthesis, biological assessment, and computational studies of triazoles as drugs, exploring the potential therapeutic significance of triazoles.

Green preparation of new pyrimidine triazole derivatives via one-pot multicomponent reactions of guanidine.

In this research the goal was to produce novel pyrimidine triazole compounds in high yields using triethylamin as an efficient catalyst. These new compounds were synthesized by using multicomponent reaction of aldehydes, guanidine, electron deficient acetylenic compounds, tert-butyl isocyanide and hydrazonoyle chloride in aqueous media. Due to the presence of an NH group, which was assessed using two different methodologies, newly synthesized pyrimidine triazoles have antioxidant properties. Additionally, the antibacterial activity of newly created pyrimidine triazoles was assessed using the disk distribution method with two different types of Gram-positive bacteria and Gram-negative bacteria, demonstrating that the use of these compounds prevented the growth of bacteria. Applied to the preparation of pyrimidine triazole derivatives, this method has short reaction times, high product yields, and the ability to separate catalyst and product using simple procedures.

Biomonitoring and risk assessment of human exposure to triazole fungicides.

Risk assessment and biomarkers were evaluated in volunteers exposed to triazole fungicides in southern Minas Gerais, Brazil. Volunteers were divided into two groups: occupationally and environmentally exposed to pesticides (n = 140) and those unexposed (n = 50) from urban areas. Urine samples were analyzed by GC-MS for triazoles, and samples from men and women in the exposed group were quantified. Groups were further stratified by sex to evaluate the biomarkers results. Oxidative stress was indicated by biomarker analysis for occupationally exposed men with elevated malondialdehyde levels and reduced superoxide dismutase and catalase activity (p < 0.0001). Bile acid levels were also elevated in the exposed group (p < 0.0001). Biomarkers in this study suggest recent, reversible changes due to pesticide exposure. Liver enzyme levels showed no significant differences. The highest Estimated Daily Intake for epoxiconazole ranged from 0.534 to 6.31 µg/kg-bw/day for men and 0.657-8.77 µg/kg-bw/day for women in the exposed group. Considering the highest detected urinary triazole value, the calculated Hazard Quotient for epoxiconazole was 0.789 for men and 1.1 for women. Results indicate a health risk associated with environmental triazole exposure, highlighting the importance of biomonitoring in risk assessment to prevent intoxication and assist in mitigating adverse health effects from chronic pesticide exposure.

Novel hybrids of 1,2,3-triazole-benzoxazole: design, synthesis, and assessment of DprE1 enzyme inhibitors using fluorometric assay and computational analysis.

Decaprenylphosphoryl-ß-D-ribose-oxidase (DprE1), a subunit of the essential decaprenylphosphoribose-2'-epimerase, plays a crucial role in the synthesis of cell wall arabinan components in mycobacteria, including the pathogen responsible for tuberculosis, Mycobacterium tuberculosis. In this study, we designed, synthesised, and evaluated 15 (BOK-1-BOK-10 and BOP-1-BOP-5) potential inhibitors of DprE1 from a series of 1,2,3-triazole ligands using a validated DprE1 inhibition assay. Two compounds, BOK-2 and BOK-3, demonstrated significant inhibition with IC50 values of 2.2 ± 0.1 and 3.0 ± 0.6 µM, respectively, whereas the standard drug (TCA-1) showed inhibition at 3.0 ± 0.2 µM. Through molecular modelling and dynamic simulations, we explored the structural relationships between selected 1,2,3-triazole compounds and DprE1, revealing key features for effective drug-target interactions. This study introduces a novel approach for designing ligands against DprE1, offering a potential therapeutic strategy for tuberculosis treatment.

Identification of 15 (BOK-1­BOK-10 and BOP-1­BOP-5) potent inhibitors of DprE1 enzyme from 1,2,3-triazole ligands.BOK-2 and BOK-3 exhibited significant DprE1 inhibition with IC₅₀ values of 2.2 ± 0.1 and 3.0 ± 0.6 µM, respectively.Molecular modelling and dynamic simulations elucidated key structural features for effective drug­target interactions.Novel approach introduced for designing DprE1 ligands, potentially aiding tuberculosis treatment.Findings offer promising candidates for future tuberculosis research.

Triazoles in the environment: An update on sample pretreatment and analysis methods.

Triazoles, due to their high bactericidal performance, have been widely used in the agricultural, clinical, and chemical industry. However, triazoles have been proven to cause endocrine-toxic and organ impairment in humans as a potentially toxic substance. Besides, because of the improper use and difficulty of degradation, triazoles pesticide residues left in the environment could pose a threat to the environment. Therefore, the rapid, reliable, accurate, and high-sensitivity triazoles analysis methods are significantly essential to effectively monitor their presence in various samples and safeguard human health. This review aims to summarize and update the progress of the pretreatment and analytical methods of triazole fungicides in environmental samples from 2012 to 2024. Common pretreatment methods used to extract and purify targets include simple steps (e.g., protein precipitation and coated blade spray), liquid-liquid extraction, solid-phase extraction, and various microextraction methods such as liquid-phase microextraction and solid-phase microextraction, among others. Detection methods mainly include liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, supercritical fluid chromatography, sensing methods, and capillary electrophoresis. In addition, we elaborate and compare the advantages and disadvantages of different pretreatment and analytical methods, and their development prospects are discussed.

Through-space H-F coupling in a series of 4-substituted-1H-1,2,3-triazoles.

In the 1H-NMR spectra of a series of N-1 substituted 4-substituted-1H-1,2,3-triazoles that have been prepared, the lone heterocyclic ring hydrogen (H-5) appears as a singlet in all cases except those compounds that contain a 2-fluorophenyl moiety at Position 4. In those cases, H-5 is a doublet with J ~3.7 Hz. Based on computational chemistry results and geometric considerations, we attribute this splitting to through-space H-F coupling.

A New Insight Into The Huisgen Reaction: Heterogeneous Copper Catalyzed Azide-Alkyne Cycloaddition for the Synthesis of 1,4-Disubstituted Triazole (From 2018-2023).

The Huisgen cycloaddition, often referred to as 1,3-Dipolar cycloaddition, is a well-established method for synthesizing 1,4-disubstituted triazoles. Originally conducted under thermal conditions [3+2] cycloaddition reactions were limited by temperature, prolonged reaction time, and regioselectivity. The introduction of copper catalyzed azide-alkyne cycloaddition (CuAAC) revitalized interest, giving rise to the concept of "click chemistry". The CuAAC has emerged as a prominent method for producing 1,2,3-triazole with excellent yields and exceptional regioselectivity even in unfavorable conditions. Copper catalysts conventionally facilitate azide-alkyne cycloadditions, but challenges include instability and recycling issues. In recent years, there has been a growing demand for heterogeneous and porous catalysts in various chemical reactions. Chemists have been more interested in heterogenous catalysts as a result of the difficulties in separating homogenous catalysts from reaction products. These catalysts are favored for their abundant active sites, extensive surface area, easy separation from reaction mixtures, and the ability to be reused. Heterogeneous catalysts have garnered significant attention due to their broad industrial utility, characterized by cost-effectiveness, stability, resistance to thermal degradation, and ease of removal compared to their homogeneous counterparts. The present review covers recent advancements from year 2018 to 2023 in the field of click reactions for obtaining 1,2,3-triazoles through Cu catalyzed 1,3-dipolar azide-alkyne cycloaddition and the properties of the catalyst, reaction conditions such as solvent, temperature, reaction time, and the impact of different heterogeneous copper catalysts on product yield.

Significance of Triazole in Medicinal Chemistry: Advancement in Drug Design, Reward and Biological Activity.

One of the triazole tautomers, 1,2,4-triazole derivatives, has a wide range of biological activities that suggest its potential therapeutic utility in medicinal chemistry. These actions include anti-inflammatory, anti-cancer, anti-bacterial, anti-tuberculosis, and anti-diabetic effects. Using computational simulations and models, we investigate the structure-activity relationships of 1,2,4-triazoles, showing how various modifications to the triazole core yield a variety of clinical therapeutic benefits. The review highlights the anti-inflammatory effect of 1,2,4-triazoles in relation to their ability to disrupt significant inflammatory mediators and pathways. We present in-silico data that illuminate the triazoles' capacity to inhibit cell division, encourage apoptosis, and stop metastasis in a range of cancer models. This review looks at the bactericidal and bacteriostatic properties of 1,2,4-triazole derivatives, with a focus on their potential efficacy against multi-drug resistant bacterial infections and their usage in tuberculosis therapy. In order to better understand these substances' potential anti-diabetic benefits, this review also looks at how they affect glucose metabolism regulation and insulin responsiveness. Coordinated efforts are required to translate the efficacy of 1,2,4-triazole compounds in preclinical models into practical therapeutic benefits. Based on the information provided, it can be concluded that 1,2,4-triazole derivatives are a promising class of diverse therapeutic agents with potential utility in a range of disorders. Their development and improvement might herald a new era of medical care that will be immensely advantageous to both patients and the medical community as a whole. This comprehensive research, which is further reinforced by in-silico investigations, highlights the great medicinal potential of 1,2,4-triazoles. Additionally, this study encourages more research into these substances and their enhancement for use in pharmaceutical development.

Mono- and bis(steroids) containing a cyclooctane core: Synthesis, antiproliferative activity, and action on cell cytoskeleton microtubules.

Steroid dimers of natural and synthetic origin possess an unusual and complex molecular architecture that may lead to the realization of peculiar effects in biological systems, in particular in different cancer cell lines. In the present work, diastereoselective ring-opening of mono- and polyoxiranes, containing a cyclooctane core, by azide-anion was performed to yield a series of azidoalcohols with different types of symmetry. The products were involved in copper-catalyzed azyde-alkyne cycloaddition (CuAAC) reaction with ethinylestradiol and ethinyltestosterone, and the resulting steroids and steroid dimers with triazole linkers were screened for their antiproliferative activity via (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide) assay. All the compounds revealed cytotoxicity toward several cancer cell lines. The effect of the most potent compound, containing two estradiol moieties, on the microtubules (MT) dynamics was investigated by immunofluorescent microscopy. The disruption of the majority of interphase cell cytoplasmic MT and mitotic event disturbances in the presence of the studied compound were observed. The latter effect caused the appearance of numerous multinucleated cells.

1,2,3-Triazole-based esters and carboxylic acids as nonclassical carbonic anhydrase inhibitors capable of cathepsin B inhibition.

Herein, we report the design and synthesis of a library of 28 new 1,2,3-triazole derivatives bearing carboxylic acid and ester moieties as dual inhibitors of carbonic anhydrase (CA) and cathepsin B enzymes. The synthesised compounds were assayed in vitro for their inhibition potential against four human CA (hCA) isoforms, I, II, IX and XII. The carboxylic acid derivatives displayed low micromolar inhibition against hCA II, IX and XII in contrast to the ester derivatives. Most of the target compounds showed poor inhibition against the hCA I isoform. 4-Fluorophenyl appended carboxylic acid derivative 6c was found to be the most potent inhibitor of hCA IX and hCA XII with a KI value of 0.7 µM for both the isoforms. The newly synthesised compounds showed dual inhibition towards CA as well as cathepsin B. The ester derivatives exhibited higher % inhibition at 10-7 M concentration as compared with the corresponding carboxylic acid derivatives against cathepsin B. The results from in silico studies of the target compounds with the active site of cathepsin B were found in good correlation with the in vitro results. Moreover, two compounds, 5i and 6c, showed cytotoxic activity against A549 lung cancer cells, with IC50 values lower than 100 µM.

Benzenesulfonamides functionalized with triazolyl-linked pyrazoles possess dual cathepsin B and carbonic anhydrase inhibitory action.

The design and synthesis of a library of 21 novel benzenesulfonamide-bearing 3-functionalized pyrazole-linked 1,2,3-triazole derivatives as dual inhibitors of cathepsin B and carbonic anhydrase enzymes are reported. The target 1,2,3-triazole-linked pyrazolic esters (16) were synthesized by the condensation of 1,2,3-triazolic diketo esters with 4-hydrazinobenzenesulfonamide hydrochloride, and these were further converted into the corresponding carboxylic acid (17) and carboxamide (18) analogs. The synthesized compounds were assayed in vitro for their inhibition potential against human carbonic anhydrase (hCA) isoforms I, II, IX, and XII. They were found to be potent inhibitors at the low nanomolar level against the cancer-related hCA IX and XII and to be selective towards the cytosolic isoform hCA I. The physiologically important isoform hCA II was potently inhibited by all the newly synthesized compounds showing KI values ranging between 0.8 and 561.5 nM. The ester derivative 16c having 4-fluorophenyl (KI = 5.2 nM) was the most potent inhibitor of hCA IX, and carboxamide derivative 18b (KI = 2.2 nM) having 4-methyl substituted phenyl was the most potent inhibitor of hCA XII. The newly synthesized compounds exhibited potent cathepsin B inhibition at 10-7 M concentration. In general, the carboxamide derivatives (18) showed higher % inhibition as compared with the corresponding ester derivatives (16) and carboxylic acid derivatives (17) for cathepsin B. The interactions of the target compounds with the active sites of cathepsin B and CA were studied through molecular docking studies. Further, the in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of the target compounds were also studied.