Search

Fused triazoloquinolines have been prepared starting from ( E )-3-(2-nitrophenyl)-1-aryl-prop-2-en-1-ones and sugar or benzyl azides in a sequential [3+2] cycloaddition reaction, followed by one pot Pd–C assisted reduction, cyclization and aromatization. The triazolyl fused quinolines with N 1 -glycosyl substituents as unnatural nucleosides have inherent potential to generate a library of compounds for bioevaluations.

A series of 4-alkylaminoaryl phenyl cyclopropyl methanones (6a–6u and 8a–8c) were synthesized from 4-fluorochalcones (3a and 3b) by cyclopropanation of double bond followed by nucleophilic substitution of F with different amines. The compounds were screened for their antitubercular and antimalarial activities against Mycobacterium tuberculosis H37Rv and Plasmodium falciparum 3D7 strains in vitro respectively. Several compounds (6a, 6d–6h, 6p, 6q and 8a–8c) exhibited good in vitro antitubercular activities with MIC values 3.12–12.5 μg/mL and preferentially inhibited the growth of P. falciparum in vitro (4a, 4c, 6a–6d, 6f, 6s, 8a and 8c) with IC50 as low as 0.080 and 0.035 μg/mL and SI values 4975 and 6948, respectively. Molecular docking studies and in vitro evaluation against FAS-II enzymes using reporter gene assays were carried out to elucidate the mode of action of these molecules. Two compounds 4a and 6g showed significant inhibition at 25 μM concentration of the compound.

Diversity-oriented synthesis of structurally different, novel and small drug like molecules based on 1,4,5-trisubstituted 1,2,3-triazoles is developed in a streamlined sequence of different sets of reactions. The method involves the use of simple, readily available and highly economical substrates and reagents. The molecules developed herein have potential to be exploited either as chemotherapeutic agents or as scaffolds for other biologically active compounds.

Filariasis is caused by thread-like nematode worms, classified according to their presence in the vertebrate host. The cutaneous group includes Onchocerca volvulus, Loa loa and Mansonella streptocerca; the lymphatic group includes Wuchereria bancrofti, Brugia malayi and Brugia timori and the body cavity group includes Mansonella perstans and Mansonella ozzardi. Lymphatic filariasis, a mosquito-borne disease, is one of the most prevalent diseases in tropical and subtropical countries and is accompanied by a number of pathological conditions. In recent years, there has been rapid progress in filariasis research, which has provided new insights into the pathogenesis of filarial disease, diagnosis, chemotherapy, the host–parasite relationship and the genomics of the parasite. Together, these insights are assisting the identification of novel drug targets and the discovery of antifilarial agents and candidate vaccine molecules. This review discusses the antifilarial activity of various chemical entities, the merits and demerits of antifilarial drugs currently in use, their mechanisms of action, in addition to antifilarial drug targets and their validation.

1,4-Disubstituted-1,2,3-triazoles (3–27) have been synthesized by [3+2] cycloaddition of different 2-(azidomethyl)-dihydronaptho(benzo)furans (2a, 2b, 2c and 2d) with different alkynes. All the compounds were screened for antitubercular activity against Mycobacterium tuberculosis H37Rv. Compounds 2a, 7, 9, 12 and 14 exhibited antitubercular activities with MIC ranging from 12.5 to 3.12 μg/ml.

Identification of compounds distinguishing between NAD+ and ATP-dependent ligases is a key factor to discover new antimicrobials. Based on virtual screening experiments a series of hydroxamates distinguishing between the above two classes of enzymes are synthesized. The specificity of the compounds for the bacterial LigA was tested in vivo involving a temperature sensitive LigA deficient E. coli GR501 strain rescued with the M. tuberculosis LigA (MtuLigA) and a wild type S. typhimurium and its LigA-strain rescued with T4 ligase. The compounds exhibit similar specificity for the NAD+-dependent ligases. In vitro assays involving the MtuLigA and the human DNA ligase I enzymes show that two compounds are ∼8-fold specific at low μM concentrations. Ethidium bromide displacement assays indicate that the compounds do not exhibit general interactions with DNA. The overall study suggests that hydroxamates have the potential to be developed as novel antibacterials.

A series of dispiro-cycloalkanones were synthesized using the “Corey Chaykovsky” reaction of α,α′-(E,E)-bis(benzylidene)-cycloalkanones/methanone in good yields. The compounds were evaluated for their in vitro antituberculosis activity against M. tuberculosis H37Rv and screened in silico. Some selected compounds were screened for mycobacterial NAD+-dependent DNA ligase inhibitory activity. Two of the compounds showed good in vitro antitubercular and NAD+-dependent DNA ligase inhibitory activity along with good correlation to in silico results.