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Microwave-assisted Green Synthesis and Integrated Bioinformatics Study Reveal Curcumin Analogs Dibenzylidene-cyclohexanones as Novel Potential Anti-Tuberculosis Agents
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Prajona Marbun2 , 3
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Rosalina Diani Prima Anargya2 , 3
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Ibnu Rahmadiansyah3
Muthia Rahayu Iresha2
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Hendra Gunosewoyo4
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Muhammad Tahir Akhtar5
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Authors Info & Affiliations
Abstract
Introduction
Tuberculosis (TB) remains a major global health challenge, further complicated by drug resistance and comorbidities. This study investigates curcumin analogues, dibenzylidene-cyclohexanones, as potential multitarget anti-TB agents.
Methods
Nine benzylidene cyclohexanone derivatives were synthesized using microwave-assisted techniques (yields: 23–81%). Their potential activities were evaluated through molecular docking against key Mycobacterium tuberculosis (Mtb) enzymes and supported by network pharmacology analysis focused on TB-related pathologies.
Results
The benzylidene cyclohexanone analogs A-135 (81%), A-144 (58%), and A-154 (30%), synthesized efficiently via microwave-assisted green chemistry, exhibited superior multitarget binding affinities against key Mtb enzymes—A-135 (MtFabH, pantothenate synthetase), A-144 (MurE, DprE1, PTPs), and A-154 (Ddn, GlmU, Pks13)—with halogen substituents enhancing interactions through halogen bonds and lipophilicity; network pharmacology further revealed 294 overlapping TB-related targets and identified NF-κB1, STAT3, STAT1, and PTGS2 as key hubs mediating their multitarget therapeutic potential modulating TB clinical manifestation in human body.
Discussion
They exhibited superior multitarget binding affinities against key Mtb enzymes, A-135 (MtFabH, pantothenate synthetase), A-144 (MurE, DprE1, PTPs), and A-154 (Ddn, GlmU, Pks13)—with halogen substituents enhancing interactions through halogen bonds and lipophilicity; network pharmacology further revealed 294 overlapping TB-related targets and identified NF-κB1, STAT3, STAT1, and PTGS2 as key hubs mediating their multitarget therapeutic potential, modulating TB clinical manifestation in the human body.
Conclusion
A-135, A-144, and A-154 demonstrate promising multitarget anti-TB activity and potential as adjuvant therapies to complement existing treatments, especially for managing drug resistance and related comorbidities.