Innovative Thiophene Schiff Bases: Synthesis and Evaluation as Antitubercular Agents

ABSTRACT

Background:Tuberculosis (TB) is a leading airborne disease, impacting millions annually and ranking among the top ten causes of global mortality. Post-COVID-19, TB incidence has increased due to its pulmonary nature, which facilitates infection spread. Current TB treatments primarily control rather than prevent infection and are associated with mycobacterial resistance and significant side effects. Purpose:This study aims to design and evaluate thiophene based Schiff bases as potential antitubercular agents targeting polyketide synthase 13 (Pks 13), crucial for mycolic acid production and less prone to resistance. Materials and Methods:Thiophene-based Schiff bases were designed based on Structure-Activity Relationship (SAR) analysis and subjected to in silicoapproaches, including molecular docking against Pks 13. Compounds with the best docking scores underwent further in silicoanalysis (ADME, drug-likeness, toxicity). These compounds were synthesized, recrystallized, characterized and evaluated for in vitroantitubercular activity using the Microplate Alamar Blue Assay (MABA). Results:Compounds Ca3 and Ca5 had the best docking scores (-8.6 and -8.4 kcal/mol) and showed significant antitubercular activity in vitroat 25 μg/mL and 12 μg/mL, respectively. In silicoand in vitroresults correlated well, indicating strong binding affinity and potency against Pks 13. Conclusion:Compounds Ca3 and Ca5 show promise as potent antitubercular agents targeting polyketide synthase 13, supporting further development and optimization of thiophene-based Schiff bases for TB treatment.

KEYWORDS

• Polyketide synthase 13
• Mycolic acids
• Docking
• In silico analysis
• MABA

Showing references and in-text citations exactly as published.

• DOI10.5530/jyp.2024.16.93Copy

RELATED ARTICLES

Matched on section and article type within this issue of JYP.

• Article · VOLUME 16, ISSUE 4Antidiabetic, Antihyperlipidemic and Protective Effect of Cupressus sempervirens L. Leaves Extract in Streptozotocin Induced Diabetic RatsSunayana Vikhe, Apeksha S. Fulsundar, Rahul Vikhe · pp. 706–713Original ArtcileSame type: Article
• Article · VOLUME 16, ISSUE 4EGFR-mTOR siRNA Loaded Immumonanoparticles for Targeted Chemotherapy of Triple Negative Breast CancerKrishnan Shalini, Rajavel Varatharajan, Hamid Shahrul, Palanimuthu Vasanth Raj, Venugopal Vijayan · pp. 714–724Original ArtcileSame type: Article
• Article · VOLUME 16, ISSUE 4Synthesis, Molecular Docking, in silico Druglikeness: In vitro Cytotoxicity Study on MCF-7 Cell Line of Quinazolin-4-one ScaffoldKavitha K, Jothikanth V, Kaniga P, Manoj Kumar S, Revathi P, Esakiprasanth R, Mohan S, Gowri Shankar NL, Jubilee R, Srinithi M, Lokesh Kumar H · pp. 725–734Original ArtcileSame type: Article
• Article · VOLUME 16, ISSUE 4Application of Reversed-Phase HPLC Method for the Simultaneous Determination of Lenacapavir and Bictegravir in Tablets Dosage FormArram Madhavi, Medidi Srinivas, Niraj Gupta · pp. 745–752Original ArtcileSame type: Article