Novel series of pyrazoline carbothioamides, acetyl pyrazoles, pyridine-3-carbonitriles, pyridine-2-carbonitriles, and nicotinonitriles were synthesized. The structures of the newly synthesized compounds were established based on their spectral data, elemental analyses and alternative synthetic routes whenever possible. Also, the newly synthesized compounds were screened for their in vitro anticancer activity against T-47D (breast cancer human cell line) and UACC-257 (melanoma human cell line) by MTT assay (a colorimetric assay for assessing cell metabolic activity). Experimental results demonstrated that compounds 3a, 4a, and 8c showed excellent in vitro activity against T-47D cell line, while compounds 3d, 6d, and 5b exhibited excellent activity against UACC-257 cell line. Molecular docking studies were performed on compound 4a, as it showed the most promising activity against T-47D cell line, using Molecular Operation Environment (MOE 2008.10) software. Also, drug-likeness, pharmacokinetics, and toxicity assessment studies were carried out.