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Synthesis of new C-dimethylated chalcones as potent antitubercular agents

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Abstract

A new class of C-dimethylated-chalcones (9a–q) were synthesized by using 2-hydroxy-3,5-dimethyl-4,6-dimethoxy acetophenone as a key intermediate. The compounds were screened for anti-tubercular activity against Mycobacterium tuberculosis strain (H37Rv) by Microplate Alamar Blue assay (MABA) method at a concentration of 100–0.8 µg/mL. The chalcones, 9a, 9b, 9c, 9k, 9o, and 9p were found to have higher antitubercular activity than the standard drugs, while the remaining compounds showed moderate activity. The antitubercular activity of the chalcones, 9b (MIC90 = 3.98 µM) and 9o (MIC90 = 3.84 µM) was found to be more than two-fold more active than the standard drugs, streptomycin (MIC90 = 10.75 µM) and ciprofloxacin (MIC90 = 9.43 µM), while their antitubercular activity was found to be more than six-fold more active than pyrazinamide (MIC90 = 25.38 µM). Further, the molecular docking studies employing Mycobacterium tuberculosis protein tyrosine phosphatase (MtbPtp) was carried out to observe docking scores.

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Acknowledgements

The authors are highly thankful to Dr. G.V. Subbaraju, CEO, Natsol Labs, Visakhapatnam for constant support and Prof. G. Rambabu, Gitam University, Hyderabad for helpful suggestions in docking studies. The authors also thank UGC for the financial assistance (F.No.39-752/2011).

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Authors and Affiliations

  1. Department of Chemistry, Acharya Nagarjuna University, Guntur, Andhra Pradesh, 522510, India

    Rambabu Anandam & Hari Babu Bollikolla

  2. Department of Chemistry, School of Technology, GITAM University, Hyderabad, Telangana, 502102, India

    Surender Singh Jadav

  3. Department of Science & Humanities, QIS College of Engineering & Technology, Prakasam District, Ongole, Andhra Pradesh, India

    Vasu Babu Ala

  4. Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Ambabari Circle, Jaipur, Rajasthan, 302039, India

    Mohamed Jawed Ahsan

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  1. Rambabu Anandam
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  2. Surender Singh Jadav
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  5. Hari Babu Bollikolla
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Correspondence to Hari Babu Bollikolla.

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Anandam, R., Jadav, S.S., Ala, V.B. et al. Synthesis of new C-dimethylated chalcones as potent antitubercular agents. Med Chem Res 27, 1690–1704 (2018). https://doi.org/10.1007/s00044-018-2183-z

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  • DOI: https://doi.org/10.1007/s00044-018-2183-z

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