Discovery of small molecule inhibitors of Mycobacterium tuberculosis ClpC1: SAR studies and antimycobacterial evaluation

Bhanot, Amritansh; Lunge, Ajitesh; Kumar, Naresh; Kidwai, Saqib; Singh, Ramandeep; Sundriyal, Sandeep; Agarwal, Nisheeth

doi:10.1016/j.rechem.2023.100904

Cited by 3 publications

(4 citation statements)

References 39 publications

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“…Nocardamin 1 H NMR (δ H , J, 500 MHz, CD 3 OD): 3.62 (4H, t, J = 6.5, H-2), 3.19 (4H, t, J = 6.5, H-6), 2.79 (4H, t, J = 6.5, H-9), 2.49 (4H, t, J = 6.5, H-10), 1.65 (4H, m, H-3), 1.53 (4H, m, H-5), 1.35 (4H, m, H-4); 13 , m, β-H of Ala 1 , and Ala 2 , β ′ -H of Ile), 1.00-0.96 (15H, m, δ-H of Leu 1 , and Leu 2 , δ-H of Ile); 13 C NMR (δ C , 125 MHz, CD 3 OD): 176.0 (C=O, Leu 2 ), 175.2 (C=O, Leu 1 ), 174.5 (C=O, Ala), 174.0 (C=O, Ile), 61.8 (α-C, Ala 1 , Ala 2 , and Ala 3 ), 60.9 (α-C, Ile), 54.7 (α-C, Leu 1 , and Leu 2 ), 41.8 (β-C, Leu 1 , and Leu 2 ), 37.7 (β-C, Ile), 25.9 (γ-C, Ile), 25.8 (γ-C, Leu 1 , and Leu 2 ), 23.2 (δ-C, Leu 2 ), 22.0 (δ-C, Leu 1 ), 19.1 (β-C, Ala 3 ), 17.7 (β-C, Ala 1 , and Ala 2 ), 15.6 (β ′ -C, Ile), and 12.2 (δ-C, Ile). The cloning, expression, and purification experiments utilized TOP10 and Rosetta 2 (DE3) strains of Escherichia coli (Novagen).…”

Section: Extraction and Isolation Of The Compounds From Streptomyces ...mentioning

confidence: 99%

“…If the activation of ClpC1 is disturbed or broken down, the protein degradation in the cells will be reduced or stopped altogether [11,12]. Due to its important role, the ClpC1 protein, which could be produced by recombination on Escherichia coli in a laboratory, has been considered a new target in the development of anti-tuberculosis agents [10,13]. Recently, naturally cyclic peptides isolated from actinomycetes and fungi, such as cyclomarin, ecumicin, lassomycin, and rufomycin, have been shown to affect the ATPase activity of ClpC1 [10,14,15].…”

Section: Introductionmentioning

confidence: 99%

“…13 C-NMR spectrum indicated seven methylene carbons at δ C 49.1 (C-2), 40.1 (C-6), 28.9 (C-9), 31.6 (C-10), 29.7 (C-5), 27.1 (C-3), 24.6 (C-4), and two carbonyl carbons at δ C 174.7 (C-8), 174.5 (C-11). In the 1H 1H COSY spectrum, crossing correlations of H-6 (δ H 3.19 with H-5 (δ H 1.53), H-5 (δ H 1.53 with H-4 (δ H 1.35), H-4 (δ H 1.35) with H-3 (δ H 1.65), and H-3 (δ H 1.65) with H-2 (δ H 3.62) were observed.The HMBC spectrum confirmed correlations from H-2 (δ H 3.62) to C-3 (δ C 27.1) and C-4 (δ C 24.6), H-6 (δ H 3.19) to C-4 (δ C 24.6), C-5 (δ C 29.7) and C-8 (δ C 174.7), H-9 (δ H 2.79) to C-8 (δ C 174.7), C-10 (δ C 31.6) and C-11 (δ C 174.5), H-10 (δ H 2.49) to C-8 (δ C 174.7), and C-9 (δ C 28.9) (Figure…”

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confidence: 99%

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Metabolites from Streptomyces aureus (VTCC43181) and Their Inhibition of Mycobacterium tuberculosis ClpC1 Protein

Tran,

Huynh,

Pham

et al. 2024

Molecules

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Tuberculosis is one of the most common infectious diseases in the world, caused by Mycobacterium tuberculosis. The outbreak of multiple drug-resistant tuberculosis has become a major challenge to prevent this disease worldwide. ClpC1 is a Clp ATPase protein of Mycobacterium tuberculosis, functioning as a chaperon when combined with the Clp complex. ClpC1 has emerged as a new target to discover anti-tuberculosis drugs. This study aimed to explore the ClpC1 inhibitors from actinomycetes, which have been known to provide abundant sources of antibiotics. Two cyclic peptides, including nocardamin (1), halolitoralin A (3), and a lactone pleurone (2), were isolated from the culture of Streptomyces aureus (VTCC43181). The structures of these compounds were determined based on the detailed analysis of their spectral data and comparison with references. This is the first time these compounds have been isolated from S. aureus. Compounds 1–3 were evaluated for their affection of ATPase activity of the recombinant ClpC1 protein. Of these compounds, halolitoralin A (1), a macrocyclic peptide, was effective for the ATPase hydrolysis of the ClpC1 protein.

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Section: Extraction and Isolation Of The Compounds From Streptomyces ...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Metabolites from Streptomyces aureus (VTCC43181) and Their Inhibition of Mycobacterium tuberculosis ClpC1 Protein

Tran,

Huynh,

Pham

et al. 2024

Molecules

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“…Do đó, protein ClpC1 đã trở thành mục tiêu quan trọng trong quá trình tìm kiếm và sàng lọc các tác nhân chống lại vi khuẩn lao một cách an toàn và hiệu quả. Protein ClpC1 được tái tổ hợp từ vi khuẩn Escherichia coli tại các phòng thí nghiệm mà không cần mức độ an toàn sinh học cao [8]. Nhiều hợp chất phân lập từ xạ khuẩn đã được phát hiện và thể hiện hoạt tính tiềm năng tác động lên quá trình thủy phân protein của ClpC1 như ecumicin, cyclomarin A, và lassomycin… [9 -11].…”

Section: đặT Vấn đềunclassified

Các hợp chất thứ cấp từ chủng xạ khuẩn actinoplanes missouriensis và hoạt tính ức chế protein ClPC1 của vi khuẩn lao mycobacterium tuberculosis

2023

jsthaui

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Từ dịch nuôi cấy chủng xạ khuẩn Actinoplanes missouriensis, hai hợp chất flufuran (1) và trehalose (2) đã được phân lập. Cấu trúc của hai hợp chất này được xác định dựa trên việc phân tích dữ liệu phổ NMR, ESI-MS và so sánh với tài liệu tham khảo. Hợp chất 1 được đánh giá khả năng tác động lên hoạt tính thủy phân ATPase của protein tái tổ hợp ClpC1. Kết quả cho thấy, chất 1 có ảnh hưởng đến quá trình thủy phân của ClpC1, một protein điều hoà quan trọng có chức năng phân hủy các protein lỗi của vi khuẩn lao Mycobacterium tuberculosis.

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CLPC1 protein inhibition, antimycobacterial, and anti‐inflammatory properties of the metabolite from Streptomyces wuyuanensis collected in Nghe An province, Vietnam

Ni,

Ninh,

Dung

et al. 2024

Vietnam Journal of Chemistry

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Streptomyces wuyuanensis A79 was isolated from the soil samples collected in Quynh Luong mangrove forest, Quynh Luu district, Nghe An province, Vietnam. This strain demonstrated antimycobacterial activity against Mycobacterium smegmatis. Compound 1 (indole‐3‐carboxylic acid) was isolated from the culture extract of S. wuyuanensis (A79). This compound displayed the affection of ATPase activity of the recombinant ClpC1 protein, a regulatory protein of Mycobacterium tuberculosis. In addition, compound 1 exhibited anti‐inflammatory activity through the inhibition of TNF‐α on LPS‐stimulated macrophage RAW264.7. This is the first time compound 1 (indole‐3‐carboxylic acid) has been isolated from S. wuyuanensis. Indole‐3‐carboxylic acid was also reported for the first time its inhibition of M. tuberculosis ClpC1 protein.

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Discovery of small molecule inhibitors of Mycobacterium tuberculosis ClpC1: SAR studies and antimycobacterial evaluation

Cited by 3 publications

References 39 publications

Metabolites from Streptomyces aureus (VTCC43181) and Their Inhibition of Mycobacterium tuberculosis ClpC1 Protein

Metabolites from Streptomyces aureus (VTCC43181) and Their Inhibition of Mycobacterium tuberculosis ClpC1 Protein

Các hợp chất thứ cấp từ chủng xạ khuẩn actinoplanes missouriensis và hoạt tính ức chế protein ClPC1 của vi khuẩn lao mycobacterium tuberculosis

CLPC1 protein inhibition, antimycobacterial, and anti‐inflammatory properties of the metabolite from Streptomyces wuyuanensis collected in Nghe An province, Vietnam

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