articles
Sonochemical synthesis of 3-arylsufonyl indole derivatives as potential inhibitors of cyclooxygenases
A small library of molecules based on the 3-arylsufonyl indole template was examined as the potential inhibitors of cyclooxygenase-2 (COX-2), an important target for the identification and development of anti-inflammatory agents. The targeted compounds were synthesized via the reaction of 2-aryl indole with arylsulfonyl chloride in the presence of In(OTf)3 under ultrasound irradiation. The short duration, mild conditions, readily available starting materials and catalyst etc. are key features of the current sulfonylation approach. When tested in vitro against COX-2 using an enzyme based assay six compounds showed good (>50 %) inhibition that was supported by the in silico docking studies. Indeed, in addition to participating in a large number of hydrophobic (especially the van der Waals) interactions these compounds formed the critical H-bond via their sulphonyl (S=O) group with ARG120 or ALA527 residue of …
5/6/2025
An ultrasound based greener approach to 1-chloropyrrolo [1, 2-a] quinoxalines as potential anti-tubercular agents
Compounds containing the 1-chloropyrrolo[1,2-a]quinoxaline framework were assessed against MtbCM (chorismate mutase) for the identification of possible anti-tubercular entities. These compounds were synthesized via the sonochemical chlorination of pyrrolo[1,2-a]quinoxalines using N-chlorosaccharin. The regioselective C-1 chlorination, mild and eco-friendly conditions, and decreased reaction time are the key aspects of the present ultrasound-assisted method, an application of which is also demonstrated. The molecular docking of synthesized compounds into the target protein MtbCM revealed that they were oriented in the loop region of MtbCM and mostly interacted with the residues in the periphery of the loop via hydrophobic interactions e.g. (i) pi-sigma with LEU130 and LEU65, (ii) pi-anion with ASP69 and (iii) pi-cation with ARG134. Furthermore, similar molecular alignment of -Cl group displaying a …
28/5/2025
New 4-Thiazolidinone-Bearing Fluoroquinolone Derivatives: Synthesis, Antimicrobial Effectiveness, Structural Characterization, and In Silico Docking Analysis
A series of ciprofloxacin-based thiazolidinone derivatives were developed and prepared by reacting active methylene compound with corresponding aldehydes. The novel compounds were analyzed using several spectroscopic techniques (FT-IR, 1H, 13C NMR and MS), and their antimicrobial properties were tested. Their minimum inhibitory concentration values were between 1.6 and 72.1 µg/mL, similar to MXF (1.9–3.5 µg/mL). From screening, the antibacterial results showed that p-chlorobenzylidene, p-dimethylaminobenzylidene, and m-methoxybenzylidene derivatives showed outstanding antibacterial activity against E. coli with zone of inhibition values of 27±0.1, 21±0.1, and 22±0.3 mm, respectively. The molecular docking predictions showed that the most active compounds have good binding affinities with E. coli DNA gyrase (7C7N). ADMET predictions were performed; the most thiazolidines possess the …
3/2025
Characterization and Analytical Method Validation for Potential Impurities of a Merchantability Drug Substance Fluoxetine HCl
A new selective and sensitive high‐performance liquid chromatography (HPLC) method was developed for the quantification of potential impurities in fluoxetine hydrochloride. Chromatographic separation was achieved on an end‐capped octadecylsilyl silica gel (Gemini‐C18 150 mm × 4.6 mm, 3.0 μm) using a gradient program with triethylamine, methanol, and water as the mobile phase at a flow rate of 1.0 mL/min and monitored at 215 nm. The run time was 60 min. The method was validated to fulfill International Conference on Harmonization (ICH Q2(R2)) requirements, and this validation included specificity, precision, linearity, limit of detection (LOD), limit of quantification (LOQ), and accuracy. The calibration curve was linear over the concentration range from LOQ to 120% with respect to sample concentration. The accuracy of the method is within the acceptable limit of 80%–120%. The results obtained …
2/2025
Sonochemical thiocyanation of pyrrolo [1, 2-a] quinoxalines: Identification of potential inhibitors of SIRT1
A series of compounds based on the 1-thiocyanatopyrrolo[1,2-a]quinoxaline framework were designed and assessed as potential inhibitors of SIRT1. A convenient access to this class of compounds was achieved via the sonochemical thiocyanation of pyrrolo[1,2-a]quinoxalines. The methodology involved use of N-thiocyanatosaccharin as a key agent under mild reaction conditions. The reaction proceeded with high regioselectivity affording the desired compounds in good to acceptable yields. The in silico docking studies suggested good interactions of these compounds with SIRT1 when majority of them formed an H-bond with GLN 345 though the most promising 3h formed H-bond with ILE347. The thiocyanato (NCS-) group of these compounds seemed to have played a key role in their interactions that formed either an H-bond through its nitrogen atom and/or participated in a pi-sulfur interaction via its sulfur atom …
15/12/2024
Wang-OSO3H catalyzed a greener approach for the synthesis of imidazo [1, 2-a] pyridin-3-amine derivatives as potential TNF-α inhibitors
The known anti-inflammatory activities of compounds containing the imidazo[1,2-a]pyridin-3-amine prompted us exploring the TNF-α inhibitory properties of a series of compounds based on this framework. These compounds were accessed via an eco-friendly approach that involved Wang-OSO3H catalyzed 3-component reaction of 2-aminopyridines, aldehydes and isocyanides in aqueous media under ultrasound irradiation. This sonochemical method furnished a range of desired imidazo[1,2-a]pyridin-3-amine derivatives in good to satisfactory yields. The intermediacy of an imine intermediate through which the reaction seemed to proceed has been demonstrated. In vitro evaluation of synthesized compounds against TNF-α led to the identification of compound 4a, 4b and 4d as initial hits with IC50 in the range ∼6.2–6.9 µM. This was further supported by the in silico docking studies that revealed TYR135, TYR227 …
15/12/2024
N-Unsubstituted 1, 2-benzothiazine 1, 1-dioxides: Pd-catalyzed one-pot sonochemical access and in silico/in vitro evaluation against MtbCM
The Pd-catalyzed one-pot sonochemical synthesis followed by in silico and in vitro evaluation of a range of N-unsubstituted 1,2-benzothiazine 1,1-dioxide derivatives is reported. The synthesis involved ultrasound assisted coupling-cyclization of 2-iodobenzenesulfonamide with terminal alkynes in the presence of (PPh3)4Pd, CuI, ZnCl2 and Et3N to afford the expected products in 73-80 % yield. This is the first example of accessing N-unsubstituted 1,2-benzothiazine 1,1-dioxides via Pd-catalyzed coupling-cyclization strategy in a single pot. Moreover, the use of mild conditions and ultrasound as the source of green energy are the main features of this approach. In silico studies suggested that all the synthesized compounds interacted with the loop near the active site of Mtb chorismate mutase or MtbCM. Indeed, these compounds showed H-bonding with residues in the hinge region of the active site loop and the …
5/4/2024
Design, synthesis and in silico docking techniques of new 1, 2, 3-triazolylpyrrolidines bearing chalcone derivatives: Discovery of potent antitubercular agents
Compounds with a pyrrolidine scaffold play an important role in organic synthesis and especially in the synthesis of bioactive organic compounds, therefore, the development of new methods for modifying this scaffold is a very interesting framework of this study. We developed a rational approach for the synthesis of 1,2,3-trazolylchalcone substituted pyrrolidines derivatives, which were then examined using a variety of spectroscopic techniques such as 1H NMR, 13C NMR, FT-IR, mass spectroscopy and elemental analysis. Biological profiles showed that compounds 5e, 5h had better antibacterial inhibitory potency against S. aureus, E. coli with zone of inhibition 34 ± 0.1, 33 ± 0.3 mm, whereas 5a, 5e showed potent antifungal activity against C. parapsilosis, A. flavus with dimeter zone of inhibition 26 ± 0.2, and 30 ± 0.2 mm respectively. Among the tested compounds 5b, and 5h were the most potent antitubercular …
1/1/2024
Synthesis, Docking and In Vitro Evaluation of Spiroindoline‐3,2’‐Quinazoline Derivatives
The 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 …
5/12/2023