1133 Synthesis and characterization of novel functionalized lactams as potent compounds against cutaneous melanoma and squamous cell carcinoma

Melanoma affects more than a million people in the United States. Regardless of skin tone, anybody may get cancer. Poor bioavailability, adverse side effects, and drug resistance have hampered current state for treating cutaneous melanoma other malignancies. Medicinal chemists want to explore different possible novel drugs increase availability, diversity-oriented synthesis (DOS) strategy aimed at producing drug-like compounds with high degree molecular diversity. One most common types antibiotics derivatives class are β-Lactams. In States, 65% all prescriptions injectable β-lactams. A number functionalized lactams were developed subjected in-vitro biological testing against CMSC (SKMeL-28 /A375) NMSC (A431/SCC-12) cell-lines. this study, cytotoxicity assessment synthesized β-Lactam revealed potent hit sub-micromolar anticancer activity IC50 values: 5.8±0.99 μM(A375), 8.7 ±1.67 μM(SKMeL-28), 8.1±1.8 μM(A431) 2.8±0.4 μM(SCC-12). Potent hits reduced clonogenicity migration dose-dependent manner, as shown by clonogenic vitro wound closure/boyden chamber experiments. Immuno-blotting/fluorescent study apoptosis markers demonstrated increased Bax, cleaved caspase-3/9 PARP levels. Protein expression many cancer targets including like ERK1/2, PI3K/Akt PIM3 downregulated. Moreover, altered autophagic pathway through modification Atg-5, Beclin-1, microtubule-associated protein 1A/1B-light chain 3 (LC3B), SQSTM1/p62. Using SwissADME web-tool, PK profiling skin-permeation (log KP), GIT absorption, Log Po/w (<5), compliancy Lipinski rule strong biodegradable properties. At last, our findings reveal prospective new lead-to-hit anti-skin agents.