Role of Vertex Index in Substructure Identification and Activity Prediction: A Study on Antitubercular Activity of a Series of Acid Alkyl Ester Derivatives

Tuberculosis (TB) is a life threatening disease caused due to infection from Mycobacterium tuberculosis (Mtb). That most of the TB strains have become resistant to various existing drugs, development of effective novel drug candidates to combat this disease is a need of the day. In spite of intensive research world-wide, the success rate of discovering a new anti-TB drug is very poor. Therefore, novel drug discovery methods have to be tried. We have used a rule based computational method that utilizes a vertex index, named `distance exponent index (D-x)' (taken x = -4 here) for predicting anti-TB activity of a series of acid alkyl ester derivatives. The method is meant to identify activity related substructures from a series a compounds and predict activity of a compound on that basis. The high degree of successful prediction in the present study suggests that the said method may be useful in discovering effective anti-TB compound. It is also apparent that substructural approaches may be leveraged for wide purposes in computer-aided drug design.

Byrsonima fagifolia Niedenzu Apolar Compounds with Antitubercular Activity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Binuclear cyclopalladated compounds with antitubercular activity: synthesis and characterization of [{Pd(C-2,N-dmba)(X)}(2)(mu-bpp)] (X = Cl, Br, NCO, N-3; bpp=1,3-bis(4-pyridyl)propane)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Triterpenes and antitubercular activity of Byrsonima crassa

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antitubercular activity of Ru (II) isoniazid complexes

Despite the resistance developed by the Mycobacterium tuberculosis (MTb) strains, isoniazid (INK) has been recognized as one of the best drug for treatment of Tuberculosis (Tb). The coordination of INH to ruthenium metal centers was investigated as a strategy to enhance the activity of this drug against the sensitive and resistant strains of MTb. The complexes trans-[Ru(NH3)(4)(L)(INH)](2+) (L = SO2 or NH3) were isolated and their chemical and antituberculosis properties studied. The minimal inhibitory concentration (MIC) data show that [Ru(NH3)(5)(INH)](2+) was active in both resistant and sensitive strains, whereas free INK (non-coordinated) showed to be active only against the sensitive strain. The coordination of INH to the metal center in both [Ru(NH3)(5)(INH)](2+) and trans-[Ru(NH3)(4)(SO2)(INH)](2+) complexes led to a shift in the INH oxidation potential to less positive values compared to free INH. Despite, the ease of oxidation of INH did not lead to an increase in the in vitro INH activity against MTb, it might have provided sensitivity toward resistant strains. Furthermore, ruthenium complexes with chemical structures analogous to those described above were synthesized using the oxidation products of INK as ligands (namely, isonicotinic acid and isonicotinamide). These last compounds were not active against any strains of MTb. Moreover, according to DFT calculations the formation of the acyl radical, a proposed intermediate in the INH oxidation, is favored in the [Ru(NH3)(5)(INH)](2+) complex by 50.7 kcal mol(-1) with respect to the free INH. This result suggests that the stabilization of the acyl radical promoted by the metal center would be a more important feature than the oxidation potential of the INH for the antituberculosis activity against resistant strains. (C) 2015 Elsevier B.V. All rights reserved.

Synthesis of new 4-isopropylthiazole hydrazide analogs and some derived clubbed triazole, oxadiazole ring systems - A novel class of potential antibacterial, antifungal and antitubercular agents

In the present study a series of 4-isopropylthiazole-2-carbohydrazide analogs, derived clubbed oxadiazole-thiazole and triazole-thiazole derivatives have been synthesized and characterized by IR, H-1 NMR, C-13 NMR, elemental and mass spectral analyses. The synthesized compounds were evaluated for their preliminary in vitro antibacterial, antifungal and antitubercular activity against Mycobacterium tuberculosis H(37)Rv strain by broth dilution assay method. The synthesized compounds 7a, 7b, 7d and 4 showed an antitubercular efficacy considerably greater than that of the parent 4-isopropyl-1,3-thiazole-2-carbohydrazide 1, suggesting that the substituted 4-isopropylthiazole-2-carbohydrazide moiety plays an important role in enhancing the antitubercular properties of this class of compounds. Compounds 2c, 3, 4, 6d, 7a and 7b exhibited good or moderate antibacterial and antifungal activity. Compounds 4 and 7b showed appreciable cytotoxicity at a concentration of 250 mu M.

Design, synthesis of some new (2-aminothiazol-4-yl)methylester derivatives as possible antimicrobial and antitubercular agents

A series of (2-aminothiazol-4-yl)methylester (5a-t) derivatives were synthesized in good yields and characterized by H-1 NMR, C-13 NMR, mass spectral and elemental analyses. The crystal structure of 5a was evidenced by X-ray diffraction study. The compounds were evaluated for their preliminary in vitro antibacterial, antifungal activity and were screened for antitubercular activity against Mycobacterium tuberculosis H37Rv strain. The synthesized compounds displayed interesting antimicrobial activity. (C) 2012 Elsevier Masson SAS. All rights reserved.

Design and synthesis of positional isomers of 5 and 6-bromo-1-(phenyl)sulfonyl]-2-(4-nitrophenoxy)methyl]-1H-benzimida zoles as possible antimicrobial and antitubercular agents

In this Letter, we report the structure activity relationship (SAR) studies on series of positional isomers of 5(6)-bromo-1-(phenyl)sulfonyl]-2-(4-nitrophenoxy)methyl]-1H-benzim idazoles derivatives 7(a-j) and 8(a j) synthesized in good yields and characterized by H-1 NMR, C-13 NMR and mass spectral analyses. The crystal structure of 7a was evidenced by X-ray diffraction study. The newly synthesized compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, (Gram-positive), Escherichia coil and Klebsiella pneumoniae (Gram-negative), antifungal activity against Candida albicans, Aspergillus flavus and Rhizopus sp. and antitubercular activity against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis, Mycobacterium fortuitum and MDR-TB strains. The synthesized compounds displayed interesting antimicrobial activity. The compounds 7b, 7e and 7h displayed significant activity against Mycobacterium tuberculosis H37Rv strain.

Novel 1,4-substituted-1,2,3-triazoles as antitubercular agents

Tuberculosis (TB) remains a pressing unmet medical need, particularly with the emergence of multidrug-resistant and extensively drug-resistant tuberculosis. Here, a series of 1,4-substituted-1,2,3-triazoles have been synthesized and evaluated as potential antitubercular agents. These compounds were assembled via click chemistry in high crude purity and in moderate to high yield. Of the compounds tested, 12 compounds showed promising antitubercular activity with six possessing minimum inhibitory concentration (MIC) values <10 μg mL^-1, and total selectivity for Mycobacterium tuberculosis (Mtb) growth inhibition. A second set of 21 compounds bearing variations on ring C were synthesized and evaluated. This second library gave an additional six compounds displaying MIC values ≤10 μg mL^-1 and total selectivity for Mtb growth inhibition. These compounds serve as an excellent starting point for further development of antitubercular therapies.

Anti-Mycobacterium tuberculosis activity of fungus Phomopsis stipata

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Synthesis and in vitro anti Mycobacterium tuberculosis activity of a series of phthalimide derivatives

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of anti-Mycobacterium tuberculosis activity of Campomanesia adamantium (Myrtaceae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

In vitro anti-Mycobacterium tuberculosis activity of some Brazilian Cerrado plants

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Increment of Antimycobaterial Activity on Lichexanthone Derivatives

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Synthesis and antitubercular evaluation of new 1,2,3-triazole derivatives of carbohydrates

Coordenação de Pessoal de Nível Superior (CAPES)