In this study, thiophene core linked to thiazole skeleton derivatives 4(a-e) were designed and synthesized via a multi-component approach, and structural elucidation was carried out via IR, NMR, LC-MS, and UV-visible spectroscopy techniques. HOMO-LUMO energies and the MEP maps of compounds 4(a- e) were obtained at the wb97xd level of theory with a 6-31 +g(d, p) basis set via Gaussian 09 w software. Compound 4e has a small energy gap, which implies that it is highly chemically reactive and more polarizable. A nonlinear optical (NLO) investigation revealed that the first-order hyperpolarizability 4e (7.0568 x 10^-30) was 19 times greater than urea. Understanding noncovalent interactions has been achieved via natural bonding orbital (NBO) studies. The cytotoxic efficacy of the title compounds was evaluated against the breast adenocarcinoma mCF-7 cell line using an MTT assay. The MTT results revealed that the electron-donating group containing 4e exhibited excellent cytotoxic activity, with an IC₅₀ of 58.06 µg/mL, which was recognized as an excellent cytotoxic inhibitor compared with that of the reference epirubicin hydrochloride (IC₅₀ =50.49 µg/mL). Furthermore, docking studies were conducted with Human 17-Betahydroxy steroid dehydrogenase type 1 mutant H221Q (PDB id: 1FDW) receptor to support the results of the biological activities.