Potato (Solanum tuberosum L.) is the most widely grown solanaceous crop in the world. In Pakistan, potato ranks fourth among food crops and fifth in total production in Pakistan. Early blight is one of the most prevalent foliar diseases of potato caused by Alternaria solani. The protective pesticides are mainly used to control potato diseases by inhibiting the respiratory enzymes of fungi. Succinate dehydrogenase (SDH) enzyme is a potential drug target due to its importance in tricarboxylic acid cycle and electron transport chain. SDH inhibitors (SDHIs) particularly impede fungal respiration; therefore plays a vital role in integrated disease management. However, the emergence of the resistance against SDHIs has reduced their efficacy. In the present research work, computer aided drug designing (CADD) was integrated with plant pathology to design novel fungicide candidates against the early blight of potato. A. solani was isolated from symptomatic potato leaves collected during the survey in Punjab, Pakistan and characterized on the morphological and molecular basis. A comparative analysis of internal transcribed spacer region 1, translation elongation factor 1 alpha, glyceraldehyde 3-phosphate dehydrogenase, and RNA polymerase II large subunit 2 gene sequences showed that the fungi were closely related to A. solani isolates. The three subunits of SDH of A. solani (AsSDH), namely AsSDHB, AsSDHC, and AsSDHD, from two isolates, PK and NL03003, were amplified from genomic DNA, cloned, and characterized. The translated coding sequences were used for the 3D structural design of SDH enzyme by homology modeling. The 3D model of AsSDH was composed of two hydrophilic proteins, (AsSDHA and AsSDHB) and two trans-membrane proteins (AsSDHC and AsSDHD) as well as prosthetic groups. The ubiquinone (UQ) binding site was comprised of the residues from AsSDHB (B-Trp234), AsSDHC (C-Arg76), and AsSDHD (D-Tyr145). In silico virtual screening was applied by using ligand based pharmacophore modeling and structure based docking approaches to screen novel antifungal scaffolds that targeted AsSDH. Pharmacophore model was used to screen 17,900,742 compounds from ZINC database. The resulting 50,000 hit compounds were docked into AsSDH model and top 1 % of the docked hits were re-scored. Based on docking energies and interactions, twelve compounds were selected. The binding modes of the twelve novel SDHI compounds revealed that most of the compounds formed hydrogen bonds with either C-Trp69, C-Ser73, or D-Tyr145, indicating that these residues play a crucial role in stabilizing the ligands in the UQ site. The selected compounds were validated via in vitro and in vivo experimental assays. In SDH activity assay, the compounds C1, C2, C6, and C10 showed higher inhibitory activities against SDH enzyme of two isolates of A. solani as compared to the negative control. In mycelial growth assay, the compound C1 (at 3 µg mL-1) was found the most effective exhibiting 82.48 % and 82.73 % growth inhibition with half maximal effective concentration (EC50) of 0.625 µg mL-1 and 0.59 µg mL-1 against PK and NL03003 isolates, respectively. For all the compounds, minimum inhibitory concentration (MIC) values ranged from 0.156 to 0.039 µg mL-1 for NL03003 and 0.0156 to 0.0195 µg mL-1 for PK isolate. In conidial germination assay, the compound C6 (at 3 µg mL-1) was the most potent with 96.67 % and 95.33 % efficacy against PK and NL03003 isolates, respectively. The compounds exhibited dose-dependent antifungal activity in mycelial growth and germination assay. The pathogenicity test showed that NL03003 isolate was more aggressive as compared to PK isolate. In detached leaf assay using NL03003 isolate, the preventive treatment of leaves with the compounds C1, C6, and C10 (at 1 µg mL-1) were found the most effective exhibiting 80.5 %, 80.4 %, and 81.49 % disease control, respectively. Under growth chamber conditions, the preventive disease control efficacy of SDHI compounds (at 1 µg mL-1) on potato plants variety Desirée showed that the application of compounds C6 and C10 decreased the lesion development by 90.33 % and 89.73 %, respectively. In curative and eradication treatment, the compound C6 was found the most potent with control efficacy of 80.44% and 74.43%, respectively. The preventive treatment (90.33 %-68.76 %) was the most effective followed by the curative (80.44 %-57.24 %) and eradication treatment (74.33 %-51.67 %). In tuber assay, preventive treatment with the compounds C1 (75.72 %), C2 (75.65 %), C6 (75.43 %), and C10 (76.27 %) strongly inhibited the dry rot. Equally, the same compounds were effective in curative and eradication treatment but with lower efficacy. Survey of potato and other crops belonging to Solanaceae family was carried out in the Punjab, Pakistan for the collection of diseased samples. The associated fungi were isolated. A total of 8 fungal species from 6 genera were isolated and characterized on the morphological and molecular basis which included; Alternaria alternata isolate 1, A. alternata isolate 2, Curvularia lunata, Fusarium solani, F. oxysporum, Geotrichum candidum, Macrophomina phaseolina, and Phytophthora infestans. The antifungal potential of the four compounds, namely C1, C2, C6, and C10, on the linear mycelial growth of isolated fungi revealed that all the compounds were potent in reducing the mycelial growth of the pathogens. We claim that this is the first attempt of using in silico strategies to develop fungicide candidates in Pakistan.