Mayank Kinger

A series of fused [1,2,4]triazolo[4,3‐b]pyridazine derivatives was synthesized via hypervalent iodine‐mediated oxidative cyclization of hydrazone intermediates using iodobenzene diacetate under mild, metal‐free conditions. This method was applied to diverse 6‐(4‐nitrophenyl)‐substituted triazolopyridazines with various aryl and heteroaryl groups, producing the target compounds in good to excellent yields with broad substrate tolerance. All compounds were characterized by FT‐IR, ¹ H NMR, ¹³ C NMR, and HRMS. Their antiproliferative activity was tested against the human triple‐negative breast cancer cell line MDA‐MB‐231 using the sulforhodamine B (SRB) assay. Compound 3c, containing a 3,4‐dimethoxyphenyl substituent, showed the highest activity, suggesting a beneficial effect of electron‐donating groups. Molecular docking against cancer‐related proteins showed favorable binding, especially with Topoisomerase IIα, though these computational results are preliminary and don't confirm the exact molecular target. This study presents an efficient synthesis strategy and identifies compound 3c as a promising lead for further biological and medicinal chemistry research.

A new series of Schiff base was synthesized via acid-catalyzed condensation of 1,3-diphenyl-1H-pyrazole-4-carbaldehydes with 4H-1,2,4-triazol-4-amine. The structures of the compounds were confirmed by ¹H and ¹³C NMR spectroscopy. Antimicrobial screening revealed that nitro and bromo substituted derivatives exhibited the most potent antibacterial and antifungal activities, with minimum inhibitory concentrations comparable to ciprofloxacin and fluconazole. Structure-activity relationship (SAR) analysis indicated that electron-withdrawing substituents significantly enhanced biological activity, while methoxy-substituted analogues displayed moderate efficacy. Molecular docking studies against bacterial DNA gyrase (PDB ID: 1KZN) demonstrated strong binding affinities (from –8.8 to –9.4 kcal/mol) and stable interactions with active-site residues, corroborating the experimental findings. Collectively, these results establish pyrazole–triazole Schiff bases as promising antimicrobial scaffolds, providing a rational basis for future pharmacological development and structural optimization.

An efficient alternative methodology for the selective functionalization of anilides has been developed through the synergistic combination of PIDA and copper(II) acetate monohydrate in acetic acid. A comparative analysis with previously reported methodologies has been carried out. The developed protocol offer a practical and effective alternative to conventional methods employing expensive or toxic heavy-metal catalysts, highlighting the versatility and cost-effectiveness of copper salts in C-H functionalization reactions. The methodology was operationally simple and proceeds under mild reaction conditions, affording ortho -functionalized products in good to excellent yields. The obtained results were found to be consistent with reported palladium and cobalt-mediated protocols, while differ from Lewis acid promoted methodologies. Additional advantages of this approach include shorter reaction times, high reaction efficiency, and a simplified work-up procedure that avoids chromatographic purification. A plausible reaction mechanism involving ortho -assisted metal chelation has also been proposed.

Chalcones are versatile scaffolds with broad pharmacological relevance, particularly as anti‐inflammatory and anti‐malarial agents. In the current investigation, a series of (3‐arylediene‐1‐phenyl‐1 H ‐pyrazol‐4‐yl)acryloyl‐4‐hydroxy‐6‐methyl‐2 H ‐pyran‐2‐one analogs/1,3‐diarylprop‐2‐en‐1‐ones were successfully synthesized, leveraging dehydroacetic acid (DHA) as the precursor molecule. The choice of DHA is strategic as it is a bioactive and highly versatile scaffold bearing a 4‐hydroxy‐6‐methyl‐2 H ‐pyran‐2‐one moiety, which enhances structural diversity and provides multiple reactive sites for functionalization. Its inherent anti‐microbial, anti‐inflammatory, and anti‐malarial potential offers an added advantage over conventional precursors, thereby increasing the likelihood of generating pharmacologically active chalcone hybrids. The synthetic protocol employed in this study involved the implementation of a Claisen condensation reaction, wherein DHA was reacted with formyl pyrazole to afford the corresponding chalcones, with yields ranging from moderate to good. The synthesized compounds were subjected to a rigorous characterization protocol, involving a battery of analytical techniques, including ¹ H‐NMR, ¹³ C‐NMR, FT‐IR, and HRMS analyses. Biological evaluation focused on anti‐malarial and anti‐inflammatory activities, while molecular docking (PyRx 0.8) was performed to explore binding interactions with cyclooxygenase‐2 (COX‐2; PDB ID: 3LN1) and enoyl‐acyl‐carrier‐protein reductase (EACPR; PDB ID: 1NHG). Notably, compound 3c emerged as the most potent one within the synthesized series, exhibiting remarkable anti‐inflammatory and anti‐malarial potency, as evidenced by its IC ₅₀ values of 7.05 ± 0.17 µM and 0.95 ± 0.06 µM, respectively. Docking studies revealed strong binding affinities and favorable molecular interactions, supporting the observed bioactivities. This study highlights chalcone–pyrazole hybrids as promising therapeutic scaffolds. In particular, compound 3c emerges as a compelling lead candidate for further optimization and preclinical investigation as a dual‐action agent against malaria and inflammation.

The aim of this study was to synthesize novel pyridine conjugates incorporating dehydroacetic acid via the Krohnke reaction and to evaluate their potential as anti-cancer agents. Materials & methods: The Krohnke reaction has previously been reported using acetic acid as the solvent, here we employed ethanol as the reaction medium. The trisubstituted pyridine derivatives were synthesized via a multistep procedure that involved the reaction of pyridinium bromide salts with chalcone derivatives of dehydroacetic acid. The synthesized hybrids were comprehensively characterized using a range of analytical techniques, including Nuclear Magnetic Resonance (NMR) spectroscopy, Fourier Transform Infrared (FT-IR) spectroscopy, and Mass Spectrometry (MS). These compounds were subjected to in vitro evaluation of their anti-cancer potential against MCF-7 (human breast cancer) and A-549 (human lung cancer) cell lines. The anti-cancer screening results indicate that the synthesized conjugates exhibit potent activity against MCF-7 cells and demonstrate moderate activity against A-549 cell lines. The analysis indicates a binding energy of -9.3 kcal/mol for the 7a derivative, which is closely comparable to that of the standard drug, which exhibits a binding energy of -9.9 kcal/mol.

A series of some new trans 2,3-dihydrofuran-linked pyrazole hybrids were synthesized from a convenient one-pot methodology. This procedure employs a sequential one-pot, two-step tandem reaction starting from pyridine, formylpyrazole, dimedone, and phenacyl bromide, with triethylamine serving as the base and proceeds efficiently in acetonitrile. The recently synthesized compounds were characterized through 1H and 13C NMR, Mass and IR spectroscopy and evaluated for their anti-inflammatory and anti-malarial potentials. Among the evaluated compounds, the derivative 4l, featuring a bromo group on the acetylphenyl and a methoxy group on the formylpyrazole phenyl ring, demonstrated potent anti-inflammatory activity with an IC50 value of 7.12 ± 0.03 μM. This potency was comparable to that of the standard drug diclofenac sodium (IC50 = 6.44 ± 0.02 μM). Additionally, 4l exhibited moderate anti-malarial properties with an IC50 value of 1.66 ± 0.04 μM, with respect to the reference drug quinine (IC50 = 0.26 ± 0.03 μM). Molecular docking studies were also performed to observe molecular interaction between the synthesized molecules and Enoyl-acyl-carrier-protein reductase (PDB ID: 1NHG) and Cyclooxygenase-2 inhibitors (3LN1). These studies provided valuable insights into the binding modes and affinities of the synthesized compounds, which may inform the design of future therapeutic agents.