Mebendazole in simultaneous combination with dexamethasone-(C21-phosphoramidate)-[anti-EGFR] generated utilizing a novel synthesis regimen: dual anti-neoplastic cytotoxicity against pulmonary adenocarcinoma (A549).

Abstract

Purpose: The short and long-term resolution of neoplastic conditions with conventional low molecular weight chemotherapeutics is frequently restricted by limitations associated dose-dependent toxic sequelae. Penetration into neoplastic cells occurs non-selectively where their intracellular concentration following simple passive diffusion from the extracellular fluid compartment becomes essentially equivalent to levels found in normal healthy cell populations residing within tissues and organ systems. Selective "targeted" delivery of conventional low molecular weight chemotherapeutics represents one molecular strategy that can both increase potency and reduce dose-dependent toxic sequela. A second strategy is the identification of synergistic or additive combinations of chemotherapeutics and pharmaceutical agents, in addition to the discovery of re-purposed pharmaceutical agents that possess anti-cancer properties.

Discussion: Mebendazole evoked anti-neoplastic cytotoxicity as both a single entity, and contributed to the potency of the covalent immunoglucocorticoid, dexamethasone-(C₂₁-phosphoramidate)-[anti-EGFR] when applied in a dual-combination challenge against populations of pulmonary adenocarcinoma (A549). In this capacity mebendazole demonstrated a role as a candidate re-purposed pharmaceutical that possessing potential as a [-i-] substitute alternative for conventional tubulin inhibitors in scenarios of idiosyncratic reactions, therapeutic resistance, or anticipated toxic sequelae; [-ii-] a new monotherapy; or [-iii-] a component in the design of new multi-therapeutic protocols.