Amit Nayyar

Recent Advances in New Structural Classes of Anti-Tuberculosis Agents

Tuberculosis (TB) is one of the most devastating diseases primarily due to several decades of neglect, and presents a global health threat of escalating proportions. TB is the second leading infectious cause of mortality today behind only HIV/AIDS. The impetus for developing new structural classes of anti-tuberculosis drugs comes from the emergence of multi-drug resistant (MDR) strains to commonly used drugs, substantially longer durations of therapy that are needed as a result of resistance, and the resurgence of disease in immuno-compromised patients. Recent years have witnessed emergence of many new structural classes of anti-TB agents, which have exhibited promising activities against drug-sensitive and drug-resistant strains of the causative organism Mycobacterium tuberculosis. These analogs ideally should decrease the overall duration of therapy with improved efficacy, and exhibit mechanisms of action different from those of existing drugs to counter the resistant strains of M. tuberculosis. This review provides a comprehensive literature compilation on advances in the new structural classes of anti-TB analogs reported during the past five years. Our discussion and observations are concentrated on chemotherapeutic potential of alphabetically listed twenty-seven new structural classes of anti-tuberculosis agents that include:- acetamides, 5-arylidene-2-thiohydantoins, benzoxazoles and benzothiazoles, benzoic acid hydrazones, benzoxazines, carbohydrates, chalcones, coumarins, deazapteridines, imidazoles, indoloquinazolinones, isothiosemicarbazones, mycobactins, 1,8-naphthyridines, phenazines, purines, pyridines, N-pyridinylsalicylamides, pyrimidines and thymidines, pyrroles, quinolines, quinoxalines, terpenes, thiadiazine thiones, thiolactomycines, toludines, and triazoles.

Substituted 4-methylquinolines as a new class of anti-tuberculosis agents

We report synthesis and anti-tuberculosis activities of a series of novel ring-substituted quinolines. The most effective compound of the series 3d (MIC=6.25 microg/mL, Mycobacterium tuberculosis H37Rv strain) was synthesized in one step; thus is an attractive lead molecule for anti-tuberculosis drug development. The results of this study represent the discovery of ring-substituted 4-methylquinolines as new class of potential anti-tuberculosis agents.

Synthesis, anti-tuberculosis activity and 3D-QSAR study of amino acid conjugates of 4-(adamantan-1-yl) group containing quinolines.

The synthesis, antimycobacterial activity and 3D-QSAR study of two series of 4-(adamantan-1-yl) group containing quinolines conjugated to amino acids are described. The most potent analogs displayed in vitro antimycobacterial activity ranging between 1.00 and 3.125 microg/mL. To understand the relationship between structure and activity, a 3D-QSAR analysis has been carried out by Comparative Molecular Field Analysis (CoMFA). The activities of molecules in the test sets were nicely predicted by the CoMFA model generated with field alignment. The best model was obtained using atom-fit alignment. Based on the molecular fields the relationships between structure and activity were easily rationalized.

Trityl-Directed Regiospecific Synthesis of 2,3-Disubstituted Bioimidazoles

Abstract We report an efficient trityl-directed regiospecific synthesis of 2,3-disubstituted-l-histdines and 2,3-disubstituted histamines starting from α-N-trifluoroacetyl-l-histidine methyl ester and α-N-trifluoroacetylhistamine respectively in five steps. # NIPER Communication no. 162.