Globally, tuberculosis (TB) stands as a prominent cause of death resulting from infectious diseases, particularly accounting for fatalities among individuals with HIV . Primarily affecting the lungs, TB spreads through the air when an infected person sneezes, coughs, or spits. As of 2022, the World Health Organization (WHO) reported an approximate annual incidence of 10.4 million new TB cases, with half a million children being infected annually, including 0.4 million cases associated with HIV/AIDS . TB surpasses other bacterial infections in terms of global mortality. WHO data indicates that approximately 95% of TB-related deaths occur in low and middle-income countries. While there are indications of a slowdown in new TB cases and deaths worldwide, recent surges in drug-resistant TB rates pose a risk of reversing these positive trends. In response, the WHO has adopted a new and comprehensive strategy, the "End TB Strategy 2016-2035," endorsed by all Member States at the World Health Assembly in 2014, guiding concerted efforts at the global, regional, and national levels . This strategy, guiding global, regional, and national efforts, emphasizes three core pillars for action: integrated patient-centered care and prevention, bold policies and supportive systems, and intensified research and innovation. Recognizing the necessity "to promote the research and knowledge-generation required to end the global tuberculosis epidemic and eliminate tuberculosis," the WHO acknowledges the ambitious goal of TB elimination . Resistant forms of tuberculosis, such as multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), pose a significant threat to global disease control efforts . Mycobacterium tuberculosis (MTB) develops resistance to both first-and second-line drug treatments, often due to non-compliance with medical care protocols. Non-adherence becomes a concern, especially considering the standard six-month treatment duration for drug-sensitive TB . In cases of resistant TB, treatment times may extend to 18-24 months, further complicated by the presence of latent MTB infection. During this latent stage, MTB cells persist in an inactive, nonreplicative state within the human body , making it particularly challenging to treat since the organism is not actively reproducing. The escalating issue of drug resistance, coupled with a rise in co-infection rates of HIV-TB, underscores the urgent need for substantial measures to advance medical treatment protocols for tuberculosis .This has facilitated researchers in discovering or designing novel drug treatments for the disease. The predominant approach to enhance resistance against diseases like TB involves identifying new drug targets within the organism. These drug targets typically encompass enzymes that play vital roles essential for the organism's survival. In this study, we collected and curated approximately 1000 anti-TB compounds, along with their experimental biological activity measured by minimum inhibitor concentration (MIC50) and inhibitor concentration (IC50) values, from various literature and databases. These compounds were divided into three classes based on their biological activity. The geometries of all the considered anti-TB compounds were optimized by Density Functional Theory (DFT) using the hybrid three-parameter Becke-Lee-Yang-Parr (B3LYP) functional with 6-31+G(d) basis set using Gaussian 09 program. Subsequently, we performed molecular docking calculations to determine docking fitness-based descriptors. DFT-based descriptors including fragment-based, quantum chemical, thermodynamic, electrostatic, topological, and geometric descriptors were calculated for structural and statistical analyses. We then performed QSAR analysis for the prediction of activities of anti-tb using docking derived molecular descriptors, it is a clustering combined methodology. We use QSAR model to validate efficacy of various DFT based descriptors on a set of 1000 anti-tb compounds with their biological activities.