Design, synthesis and anti-mycobacterial evaluation of imidazo[1,2-<i>a</i>]pyridine analogues

Khetmalis, Yogesh Mahadu; Chitti, Surendar; Wunnava, Anjani Umarani; Karankumar, Banoth; Kumar, Muthyala Murali Krishna; Murugesan, Sankaranarayanan; Chandrasekhar, K. V. G.

doi:10.1039/d1md00367d

Cited by 15 publications

(10 citation statements)

References 29 publications

(47 reference statements)

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“…The most promising compounds, 10A12 , 10A16 , 10A19 , and 10A25 with IC 50 <10 μM, were examined for toxicity to regular cells by screening the compounds on human embryonic kidney (HEK) cells. The IC 50 values of these compounds were evaluated at ten different doses (1.0 mM–1.0 μM) on HEK‐293 cells for 48 h, and cell viability was measured by MTT assay [5] . They exhibited selectivity index (SI) value >25.…”

Section: Resultsmentioning

confidence: 99%

“…The IC 50 values of these compounds were evaluated at ten different doses (1.0 mM -1.0 μM) on HEK-293 cells for 48 h, and cell viability was measured by MTT assay. [5] They exhibited selectivity index (SI) value > 25. The IC 50 values and SI values are tabulated in Table 2.…”

Section: Cytotoxicity Studiesmentioning

confidence: 99%

“…Therefore, the development of new drugs is urgent. New candidates must be able to shorten and simplify the treatment, improve tolerance, be aggressive against the multidrug‐resistant and extensively drug‐resistant strains [3–5] . The tetrahydroisoquinoline (THIQ) skeleton is an essential structural domain in plant‐derived natural alkaloids with exciting biological properties [6–8] .…”

Section: Introductionmentioning

confidence: 99%

“…New candidates must be able to shorten and simplify the treatment, improve tolerance, be aggressive against the multidrug-resistant and extensively drug-resistant strains. [3][4][5] The tetrahydroisoquinoline (THIQ) skeleton is an essential structural domain in plant-derived natural alkaloids with exciting biological properties. [6][7][8] THIQ derivatives were re-ported to possess anticancer, [9 -11] antimicrobial, [12] and antiplasmodial activities.…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, and Antimycobacterial Evaluation of Novel Tetrahydroisoquinoline Hydrazide Analogs

Kumar

Khetmalis

Nandikolla

et al. 2023

Chemistry & Biodiversity

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A series of novel 2-substituted-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carbohydrazide were designed, synthesized and structures were confirmed by analytical methods, viz., 1 H-NMR, 13 C-NMR and Mass spectrometry. Synthesized derivatives were evaluated for their anti-mycobacterial activity against Mycobacterium tuberculosis (Mtb) H37Ra. Among all the evaluated compounds, 10A25 containing biphenyl moiety exhibited significant inhibition with IC 50 4.7 μM. 10A19, with an electron-withdrawing Iodo group in the ortho position of the phenyl exhibited significant anti-tubercular activity with IC 50 8.8 μM. IC 50 values of the remaining compounds ranged from 9.2 to 73.6 μM. Molecular docking study of the significantly active compound 10A25 was performed to determine the putative binding position of the test ligand at the active site of the selected target proteins Mycobacterium tuberculosis enoyl reductase (InhA) PDB -4TZK and peptide deformylase PDB -3E3U. A suitable single crystal for one of the active compounds, 10A12, was generated and analysed to further confirm the structure of the compounds.

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Section: Resultsmentioning

confidence: 99%

Section: Cytotoxicity Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, and Antimycobacterial Evaluation of Novel Tetrahydroisoquinoline Hydrazide Analogs

Kumar

Khetmalis

Nandikolla

et al. 2023

Chemistry & Biodiversity

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“…Following the simulation procedure, which lasts for 100 ns of production, the NPT ensemble was started. The frames have been gathered and studied using the simulation interaction diagram to investigate the trajectories, which assisted in identifying uctuations [27].…”

Section: Molecular Dynamics (Md) Studiesmentioning

confidence: 99%

QSAR modelling, ADMET prediction, molecular docking and molecular dynamics studies of novel 2-amino thiazole derivatives as Aurora kinase inhibitors

Bathula

Murugesan

Ilango

2023

Preprint

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The Aurora kinase is implicated in tumor growth and several small medicines that target the Aurora kinase have been found to have strong anti-cancer effects. Quantitative structure-activity relationship (QSAR) studies on 2-amino thiazole compounds for Aurora kinase inhibitory action targeting breast cancer were conducted out by QSARINS in this study. With statistical values R2 = 0.6102, CCCtr = 0.7580, Q2 LOO = 0.6875, Q2LMO = 0.6624, CCCcv = 0.6535, R2ext = 0.7735 and CCCext = 0.8383. Best top two models created comprise five variables: Estate VSA5, PSA, MoRSEP3, MATSp5 and RDFC24. Atomic charges, atomic volume and Sanderson's electronegativity all play a part in the design and optimization of the lead. In silico docking study was performed AutoDock v4.2.6. There are eight novel compounds have been designed, the residues from the active site region, which contains both hydrophilic and hydrophobic regions, interacted with the best active site pockets of 1MQ4, predicted active molecules 1a, 2a, 3e, 4d, 5d and 6d. Hydrophobic and hydrophilic stable contacts were seen in the active site of compound 1a in Desmond's molecular dynamics simulation investigations lasting 100 ns. The stable binding of compound 1a with the 1MQ4 structure was verified by RMSD, RMSF, RoG, H-bond and SASA analyses. We suggest that the proposed compound 1a can be used as the best theoretical lead for further experimental investigation of selective inhibition. Furthermore, newly designed compounds exhibited good ADMET properties. The study will result in the development of new breast cancer inhibitors.

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Pyrazole‐Imidazopyridine Hydrazones: Synthesis, α‐Glucosidase, α‐Amylase Inhibitory Activity and Computational Studies

et al. 2023

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Diabetic complications poses major threat to mankind which found to be dangerously fatal all over the world. It is thought vital to find new class of molecules to combat diabetic problems. Thus, in continuation of our efforts in identifying new class of α‐glucosidase and α‐amylase inhibitors, a novel series of hybrid molecules comprising of imidazo[1,2‐a]pyridine and pyrazoles, i. e. (3‐(Substituted phenyl)‐1H‐pyrazol‐4‐yl)methylene)‐2,7‐dimethyl‐1H‐imidazo[1,2‐a]pyridine‐3‐carbohydrazide derivatives (8 a–m) were designed through a acyl hydrazone bridge. The compound (Z)‐N′‐({3‐[4‐(2‐Fluorobenzyloxy)phenyl]‐1H‐pyrazol‐4‐yl}methylene)‐2,7‐dimethyl‐imidazo[1,2‐a]pyridine‐3‐carbohydrazide (8 m) emerged as potent inhibitor of α‐glucosidase and α‐amylase enzyme with IC50 5.00±0.10 μg/mL and 15±0.35 μg/mL respectively. The enzyme kinetics studies revealed reversible non‐competitive mode of inhibition of 8 m against both enzymes. In addition, these compounds were subjected to detailed in‐silico studies to understand their interaction with respective target proteins.

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Design, synthesis and anti-mycobacterial evaluation of imidazo[1,2-a]pyridine analogues

Abstract: Based on the molecular hybridization strategy, thirty-four imidazo-[1,2-a]-pyridine amide (IPA) and imidazo-[1,2-a]-pyridine sulfonamide (IPS) were designed and synthesized. The structures of the target compounds were characterized using 1 HNMR, 13...

Cited by 15 publications

References 29 publications

Design, Synthesis, and Antimycobacterial Evaluation of Novel Tetrahydroisoquinoline Hydrazide Analogs

Design, Synthesis, and Antimycobacterial Evaluation of Novel Tetrahydroisoquinoline Hydrazide Analogs

QSAR modelling, ADMET prediction, molecular docking and molecular dynamics studies of novel 2-amino thiazole derivatives as Aurora kinase inhibitors

Pyrazole‐Imidazopyridine Hydrazones: Synthesis, α‐Glucosidase, α‐Amylase Inhibitory Activity and Computational Studies

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