Evaluation of Novel Spiro-Barbiturates for Potential Anticancer and Antidepressant Activities: In vitro and In vivo Studies

A BSTRACT Context: Barbituric drugs that cause an anesthetic affect positively modulate allosterically gamma-aminobutyric acid A receptors, but their usage has been discontinued due to their heavy abuse. Hence, there is growing interest to develop analogues of barbiturates that have both therapeutic benefits and less undesirable side effects. One such class of barbiturates that is synthetically formed by a closed ring at the 5 th carbon position is called spiro barbiturates (SBs), and have been shown to possess various biological functions as anticonvulsant, hypnotics, anesthetics, and anticancer activities. Aim: The aim of this study is to evaluate whether the novel synthesized SBs does have the ability as an anticancer drug, as proven in previous studies, or cause the same level of central nervous system depression as that observed with debarred barbiturates. Subjects and Methods: SB synthesized via a green approach was evaluated for its drugability quotient. In vitro studies were carried out in human colon cancer cell lines and human macrophages (THP1). In vivo studies were done on Zebrafish larvae and toxicity, angiogenesis, and behavioral assays were conducted for all four SBs. Results: In vitro studies in cancer cell lines and human macrophages showed that with an increase in concentration, spiro-barbiturates cause toxicity to both cell lines. Further, toxicity, angiogenesis, and behavioral assays showed dose-dependent variations for all four SBs, and only Meta-chloro spirobarbiturate showed potential as an anticancer and antidepressant drug. Conclusion: The synthesized SBs, though, have potential as antidepressants but their usage as drugs still needs extensive research and validation before these are proven effective for human use.