The rise of drug-resistant and emerging illness shows how important it is to find new ways for innovative therapeutic interventions. By Using existing drugs in new ways and computer-based methods, it can help speed up the process of finding and developing new medicines. This study uses these methods to create and evaluating derivatives of a drug that are already approved by the FDA, called Sulfonyl hydrazone, to see how altering its structure affects its ability to treat diseases. The derivatives have been created using of a group of small molecules with imine groups, based totally on a sulfonyl hydrazone scaffolds (YY-01, YU-02, YH-03, YK-04, YR-05) with substituted aromatic aldehydes and evaluated in silico for physicochemical properties, drug-likeness, expected bioactivity, ADME, and toxicity. Computational tools like stoptox, protox, way2drug, PASS and pkCSM platform (website) had been used to check the physical and chemical properties, drug-likeness, potential biological results of every derivative of sulfonyl hydrazone, and how far it’s absorbed, distributed, metabolized, and excreted (ADME profiles) in the body. All the five derivatives complied with Lipinski’s Rule of five, which relatively shows molecular weights present in low-to-mid 300 Da range, YY-01 displayed the finest steric bulk due to an indane fragment while YR-05 and YU-02 had been the least bulky. ADME predictions indicated favourable oral absorption potential and acceptable permeability and distribution metrics for small‑molecule leads, with limited predicted BBB/CNS penetration; metabolic profiling revealed substituent‑dependent interactions with cytochrome P₄₅₀ enzymes, notably enhanced CYP‑related interactions for the 2‑chloro bearing YK‑04 and altered clearance patterns for the bulky YY‑01. Pass and cheminformatics bioactivity scoring returned high possibilities for several therapeutic events, with core predictions inclusive of antimycobacterial and enzyme inhibitory actions and secondary symptoms spanning antibacterial, antiviral, anti-inflammatory, and anticancer outcomes; All derivatives except YU-02 showed the most powerful multi category activity profiles.YK 04 and YY 01 benefit potency optimization however require centred metabolic and safety comply with up; usual, the in silico evaluation supports the sulfonyl hydrazone derivatives as promising candidates for synthesis and experimental validation, with recommended subsequent steps consisting of in vitro ADME assays, CYP inhibition testing, and targeted toxicity studies. These Schiff base derivatives display exceptional ability for future drug improvement, highlighting how computational strategies play a key role in enhancing discovery and design of the drug and its derivatives. ...

Keywords: Rational drug design; drug repositioning or rediscovery; in-silico study; and ADME properties ...