QSAR and Molecular Docking Studies on Nitro (Triazole/Imidazole)-Based Compounds as Anti-Tubercular Agents doi.org/10.26538/tjnpr/v5i11.22
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Abstract
Tuberculosis is a chronic infectious disease which remains one of the leading causes of death worldwide. Scientists are currently engaging both experimental and theoretical methods to seek solution to this deadly disease. This work is aimed at identifying descriptors that described the anti-Mycobacterium tuberculosisH37Rv activity of nitro(triazole/imidazole)-based compounds and reliable quantitative structure activity relationship (QSAR) model were developed using selected descriptors as well as observing non-bonding interactions between studied complexes. Nineteen molecules comprising 3-nitrotriazole- and nitroimidazole- analogues were studied as anti-tubercular agents against Rv0371c from Mycobacterium tuberculosis H37Rv (PDB ID:2we9) using semi-empirical PM3 method, quantitative structure activity relation (QSAR) studies and Docking approaches. QSAR model was successfully developed, and the studies indicated that four 2D descriptors (nO, ATS3m, ATS6m and ATS7m) were important factors for the observed biological activity. Also, the studied docking studies revealed that all the studied compounds could form a stable complex with the active site of the protein with compound 10 (N-([1,1'-biphenyl]-3-yl)-2-(3-nitro-1H-1,2,4-triazol-1-yl)acetamide) forming the most stable complex. It was observed that the obtained descriptors perfectly described the anti-Mycobacterium tuberculosis activity of the studied nitro(triazole/imidazole)-based compounds and the developed QSAR model proved to be reliable by accurately predicting the experimental IC50. Nonbonding interaction between nitro(triazole/imidazole)-based compounds and Mycobacterium tuberculosis H37Rv (PDB ID: 2we9) showed that compound 10 with -8.0 kcal/mol have higher tendency to inhibit Mycobacterium tuberculosis H37Rv (PDB ID: 2we9) than other studied compounds.
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References
Asif M. A Brief Review on Antitubercular Activity of Pharmacological Active Some Triazole Analogues. Global J Res Rev. 2014; 1(3):051-058.
Riccardo M, Menico R, Davide M. Ferraris. Mycobacterium tuberculosis Pathogenesis, Infection Prevention and Treatment, Pathogens. 2020; 9(5):385.
Burel JG, Singhania A, Dubelko P, Muller J, Tanner R, Parizotto E, Dedicoat M, Fletcher TE, Dunbar J, Cunningham AF, Arlehamn CSL, Catanzaro DG, Catanzaro A, Rodwell T, McShane H, O'Shea MK, Peters B. Distinct blood transcriptomic signature of treatment in latenttuberculosis infected individuals at risk of developing active disease. Tubercul. 2021; 131:102127.
Lilienkampf A, Mao J, Wan B, Wang Y, Franzblau SG, Kozikowski AP. Structure-activity relationships for a series of quinoline-based compounds active against replicating and nonreplicating Mycobacterium tuberculosis. J Med Chem. 2009; 52(7):2109-2118.
Klopper M, Warren RM, Hayes C, Van Pittius NCG, Streicher EM, Muller B, Sirgel FA, Chabula-Nxiweni M,Hoosain E, Coetzee G, Emergence and Spread of Extensively and Totally Drug-Resistant Tuberculosis. Emerg Infect. Dis. 2013; 19(3):449-455.
Zumla A, Nahid P, Cole ST. Advances in the development of new tuberculosis drugs and treatment regimens. Nat Rev Drug Discov. 2013; 12(5):388404.
Erazua EA, Oyebamiji AK, Adeleke BB. DFT-QSAR and Molecular Docking Studies on 1,2,3-TriazoleDithiocarbamate Hybrids as Potential Anticancer Agents. Phys Sci Int J. 2018; 20(4):1-10.
Hafez HN, Abbas HA, El-Gazzar AR. Synthesis and evaluation of analgesic, anti-inflammatory and ulcerogenic activities of some triazolo-and 2-pyrazolyl-pyrido [2, 3-d]-pyrimidines. Acta Pharm. 2008; 58(4):359-378.
Demaray JA, Thuener JE, Dawson MN, Sucheck SJ. Synthesis of triazole-oxazolidinones via a one-pot reaction and evaluation of their antimicrobial activity. Bioorg Med Chem Lett. 2008; 18(17):4868-71
Bay HA, Quaddouri B, Guaadaoui A, Touzani R, Benchat N, Hamal A, Taleb M, Bellaoui M, Kadiri SE. Synthesis and Biological Activity of New Triazole Compounds, Drug Design Disc. 2010; 7(1):41-45.
Mukherjee T and Boshoff H. Nitroimidazoles for the treatment of TB: past, present and future. Med Chem. 2011;
(11):1427-1454.
Mai A, Sbardella G, Massa S, Novellino E, Greco G, Lavecchia A, Musiu C, La Colla M, Murgioni C, La Colla P, Loddo R. Structure-based design, synthesis, and biological evaluation of conformationally restricted novel 2-alkylthio-6-[1-(2,6-difluorophenyl)alkyl]-3,4-dihydro-5-alkylpyrimidin-4(3H)-ones as non-nucleoside inhibitors of HIV-1 reverse transcriptase. J Med Chem. 2001; 44(16):2544-2554.
Qingzhi G, Lulu Y, Yongqiang Z. Pharmacophore Based Drug Design Approach as a Practical Process in Drug Discovery. Curr Comput Aided Drug Des., 2010; 6(1):37-49.
Huang S and Zou S. Advances and challenges in proteinligand docking. Int J Mol Sci. 2010; 11(8):3016-3034.
Meng EC, Shoichet BK, Kuntz ID, Meng EC, Shoichet BK, Kuntz ID. J Comput Chem. 1992; 13(4):505-524.
Lipnick RL. Correlative and Mechanistic QSAR Models in Toxicology. SAR and QSAR in Environ Res. 1999; 10(2):239-248.
Papadopoulou MV, Bloomer WD, Rosenzweig HS. The antitubercular activity of various nitro(triazole/imidazole)-based compounds. Bioorg Med Chem. 2017; 25(21):6039-6048.
Akintelu SA, Folorunso AS, Oyebamiji AK. Phytochemical and antibacterial investigation of Moringa oleifera seed:
experimental and computational approaches. Ecletica Quim J. 2021; 46(2):17-25.
Oyebamiji AK, Akintelu SA, Amao OP, Kaka MO, Morakinyo AE, Amao FA, Semire B. Dataset on Theoretical Bio-Evaluation of 1,2,4-Thiadiazole-1,2,4-Triazole Analogues against Epidermal Growth Factor Receptor Kinase down Regulating Human Lung Cancer. Data in Brief. 2021; 37:107234
Trott O and Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem.2010; 31(2):455-461.
Oyebamiji AK, Fadare OA, Semire B. Anti-gastric cancer activity of 1,2,3-triazolo[4,5-d]pyrimidine hybrids (1,2,3-
TPH): QSAR and molecular docking approaches. Heliyon. 2020; 6(3):e03561.
Semire B, Oyebamiji AK and Odunola OA. Tailoring of Energy Levels in (2Z)-2-cyano-2-[2-[(E)-2-[2-[(E)-2-p-tolyl)vinyl]thieno[3,2-b]thiophen-5-yl]vinyl]pyran-4-ylidene]acetic acid Derivatives via Conjugate Bridge and Fluorination of Acceptor units for Effective D-π-A DyeSensitized Solar Cells: DFT-TDDFT Approach, Research on Chemical Intermediates, 2017; 43:1863-1879.
Oyebamiji AK, Tolufashe GF, Oyawoye OM, Oyedepo TA, Semire B. Biological Activity of Selected Compounds from
Annona muricata Seed as Antibreast Cancer Agents: Theoretical Study. J Chem. 2020; vol. 2020, Article ID 6735232:1-10.
Oyewole RO, Oyebamiji AK, Semire B. Theoretical calculations of molecular descriptors for anticancer activities of 1, 2, 3-triazole-pyrimidine derivatives against gastric cancer cell line (MGC-803): DFT, QSAR and docking approaches. Heliyon 2020; 6(5):e03926.
Oyebamiji AK, Akintelu AS, Mutiu OA, Adeosun IJ, Kaka MO, Olotu TM, Soetan AE, Adelowo JM, Semire B. InSilico Study on Anti-cancer Activity of Selected Alkaloids from Catharanthus roseus. Trop J Nat Prod Res. 2021; 5(7):1315-1322.
Olasupo SB, Uzairu A, Shallangwa G, Uba SJ. Quantitative Structure-Activity Relationship (QSAR) Studies and Molecular docking Simulation of Norepinephrine Transporter (NET) Inhibitors as Anti-psychotic Therapeutic Agents. Turk Chem Soc Sect A Chem. 2019; 7(1):179-196.
Adegoke RO, Oyebamiji AK, Semire B. Dataset on the DFT-QSAR, and docking approaches for anticancer activities of 1, 2, 3-triazole-pyrimidine derivatives against Human Esophageal Carcinoma (EC-109), Data in Brief.2020; 31:105963