title: Fluorination of an antiepileptic drug: A self supporting transporter by oxygen enrichment mechanism.
abstract: Drug therapy of seizures involves producing high levels of antiepileptic drugs in the blood. Drug must enter the brain by crossing from the blood into the brain tissue, called a transvascular route (TVR). Even before the drug can reach the brain tissue, factors such as systemic toxicity, macrophage phagocytises and reduction in oxygen content limit the success of this TVR. Encapsulating the drug within a nano scale delivering system, synthesising drugs with low molecular weight are the best mechanisms to deliver the drug to the brain. But through this article, we have explored a possibility of attaching a molecule 4-(trifluoromethyl) benzoic acid (TFMBA), that possess more number of fluorine atom, to benzodiazepine (BDZ) resulting in an ionic salt (S)-(+)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine5,11(10H,11aH)-dione with 4-(trifluoromethyl)benzoic acid. By this way, reducing the toxicity of BDZ than the conventional anti-epileptic drugs (AEDs), increasing the solubility, reducing the melting point, enriching the TVR with excess oxygen content with the support of fluorine. With all these important prerequisites fulfilled, the drug along with the attached molecule is expected to travel more comfortably through the TVR without any external support than any other conventional AEDs. FTIR, (1)H NMR, (13)C NMR, HRMS spectroscopy, HRTEM and In vitro cytotoxicity analysis supports this study.
authors.affiliation: PG & Research Department of Physics, National College (Affiliated to Bharathidasan University), Karumandapam, Tiruchirapalli 620 001, Tamil Nadu, India. Electronic address: natchimuthu88@gmail.com.
authors.forename: V
authors.initials: V
authors.lastname: Natchimuthu
authors.affiliation: Departamento de Física Applicada, UniVersitad de Cantabria, AVda, Los Castros 39005, Santander, Spain. Electronic address: amorosj@ccaix3.unican.es.
authors.forename: J
authors.initials: J
authors.lastname: Amoros
authors.affiliation: PG & Research Department of Physics, National College (Affiliated to Bharathidasan University), Karumandapam, Tiruchirapalli 620 001, Tamil Nadu, India. Electronic address: suga_ravi@yahoo.co.in.
authors.forename: S
authors.initials: S
authors.lastname: Ravi
mesh_terms: D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D001570:Benzodiazepinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002220:Carbamazepine / Q000633:toxicity; D005632:Fructose / Q000031:analogs & derivatives / Q000633:toxicity; D054879:Halogenation; D006801:Humans; D061986:MCF-7 Cells; D008970:Molecular Weight; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D012995:Solubility; D013237:Stereoisomerism; D014050:Toluene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D000077236:Topiramate; D044366:Transition Temperature
chemical_list: C000610575:2,3-dihydro-1H-pyrrolo(2,1-c)(1,4)benzodiazepine-5,11(10H,11aH)-dione; D000927:Anticonvulsants; D001570:Benzodiazepinones; D011758:Pyrroles; D000077236:Topiramate; D005632:Fructose; D002220:Carbamazepine; D014050:Toluene; C028383:4-(trifluoromethyl)benzoic acid
keywords: Benzodiazepine; Blood–brain barrier; Cyto-toxicity evaluation; Epilepsy; Seizures; Self-supporting transporter mechanism; Transvascular route