ORIGINAL RESEARCH Exploring the relationship between the physico-chemical parameters and anti-tubercular activity of quinoline-3-carboxylic acids: a QSAR approach Ravichandran Veerasamy • Sridevi Chigurupati • Shalini Sivadasan • Dhanaraj Sokkalingam Arumugam • Harish Rajak • Suresh Kumar Krishnan Received: 18 December 2013 / Accepted: 6 July 2014 Ó Springer Science+Business Media New York 2014 Abstract Resistance of Mycobacterium tuberculosis strains is the major issue for many antimycobacterial agents. Quinoline compounds serve as antimycobacterial agents with encouraging anti-tubercular activity. A linear quantitative structure–activity relationship (QSAR) model is presented for modeling and predicting anti-tubercular activity of quinolone-3-carboxylic acids. The model was produced on the database consisting of 34 quinoline-3 carboxylic acids using stepwise multiple linear regression technique. The developed QSAR model was evaluated for statistical significance and was validated using internal and external validation. Physiochemical descriptors serve as the first line guidance for the design of potent and novel anti- tubercular agents. The key conclusion of this study is that the calculated molar refractivity, number of hydrogen bond donors, steric parameters B1 R1 and L R1 , also the presence of NO 2 in the position of R significantly influence the anti- tubercular activity of novel quinoline-3 carboxylic acid derivatives. Keywords Anti-tubercular agents  Tuberculosis  Quantitative structure activity relationship  Quinoline-3-carboxylic acid derivatives Introduction Tuberculosis is the most commonly encountered myco- bacterial disease. The WHO considers tuberculosis as one of the most dangerous chronic communicable disease. Resistance of Mycobacterium tuberculosis strains is the major issue for many antimycobacterial agents. Effective new anti-TB drugs with new mechanism of action have not been seen in last 40 years. In spite of severe toxicity on repeated dosing of Isoniazid, it is still considered as first line drug for the treatment of tuberculosis. It has been estimated that nearly 8 million people develop active TB every year and approximately 5,500 deaths per day (www. who.int/mediacentre/factsheets/fs104/en//). Tuberculosis has been treated with combination therapy for over 50 years. Drugs are not used singly (except in latent TB or chemoprophylaxis), and regimens that use only single drugs result in the rapid development of resistance and treatment failure (Wang et al., 2006). The rationales for using multiple drugs to treat TB are based on simple probability. In addition to the obvious risks (i.e., known exposure to a patient with MDR-TB), risk factors for MDR-TB include male sex, HIV infection, previous incarceration, failed TB treatment, failure to respond to standard TB treatment, and relapse fol- lowing standard TB treatment. People with HIV and latent TB infection need treatment as soon as possible to prevent them from developing TB disease. People with HIV who have latent TB infection are much more likely to progress to TB disease than people without HIV. Unfortunately, some people with HIV do not know that they are infected with TB. Simi- larly, one in five people with TB disease are unaware of their HIV status, although HIV status reporting for people with TB is improving. CDC recommends that anyone who has TB disease/suspected of having TB disease, or in a contact of a TB patient, should be tested for HIV (Breen et al., 2006). R. Veerasamy (&)  S. Chigurupati  S. Sivadasan  D. Sokkalingam Arumugam Pharmaceutical Chemistry Unit, Faculty of Pharmacy, AIMST University, 08100 Semeling, Kedah, Malaysia e-mail: phravi75@rediffmail.com; sameshyaravi@gmail.com H. Rajak SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur, India S. K. Krishnan Medicinal Chemistry Research Laboratory, KMCH College of Pharmacy, Coimbatore, India 123 Med Chem Res DOI 10.1007/s00044-014-1167-x MEDICINAL CHEMISTR Y RESEARCH