In the present study, five derivatives have been designed to be synthesized as possible mutual prodrugs for 5-Fluorouracil (5-FU) and non steroidal anti-inflammatory drugs (NSAIDs) to selectively deliver the drugs into the cancer cells. The synthesis of the target compounds were accomplished following multistep reaction procedures, the chemical reaction followed up and the purity of the products were checked by TLC. The structure of the final compounds and their intermediates were confirmed by their melting points, infrared spectroscopy and elemental microanalysis, the hydrolysis of compound III was studied using HPLC technique. According to the results mentioned above, compounds (I−V) can be good candidates as possible mutual prod

 5-Fluorouracil is one of the commonly used chemotherapy drugs in anticancer therapy; unfortunately treatment with 5-FU by solely has many drawbacks  low lipophilicity, low permeability, low molecular weight, and its relatively poor plasma protein binding; also a brief half-life therefore frequent administration is required to maintain the optimal therapeutic plasma level which in addition to its poor selectivity, drug resistance and limited penetration to cancer cells; leads to increased incidence of side-effects to healthy cells/tissues and low response rates. In order to minimize these drawbacks; 5-FU was chemically  conjugated with pyrrolidine dithiocarbamate (PDTC) in a mutual prodrug moiety (S-(9H-purin-6-yl) 3-(

On the basis of known coumarin-based prodrug system, a novel coumarin-based mutual prodrug of 5-fluorouracil and dichloroacetic acid was designed, synthesized and evaluated as a promising oral chemotherapeutic agent basing on in vitro stability study in HCl buffer (pH 1.2) and in phosphate buffer (pH 7.4), as well as in vitro release study in human serum. The chemical structure of prodrug was confirmed by analyzing its FTIR, ¹H NMR, ¹³C NMR and MS-ESI spectra. The results of in vitro kinetic study indicated that the prodrug was significantly stable in HCl and in phosphate buffers, and was hydrolyzed in human serum followed pseudo first order kinetics.

Keywords: Coumarin-bas

A lower extracellular pH is one of the few well-documented physiological differences between tumour and normal tissues. On the other hand, elevated glutathione (GSH) level has been detected in many tumours compared with healthy surrounding tissues. The compound II: 3-(9H-purin-6-yl-thio) carbonothionyl methyl-8-oxo-7-(2-thiophen-2-yl) acetamido-5-thia-1-azabicyclo-4-octo-ene-carboxylic acid was a cephalothin derivative contain 6-mercaptopurine (6-MP). Compound II react with general base catalysis in slightly acidic pH or with sulfhydryl nucleophiles to release the chemotherapeutic drug 6-MP. The generation of compound II was accomplished following multistep reaction procedures. The structure of compound II and its intermediate was confir

In this research, two drugs were bonded through amide and ester attachment, using lactic acid as aspacer binder, produced di pro drug such as Procain and Ciprofloxacin. Since Procain has ailocail anesthetic action and Ciprofloxacin as antibacterial drug was reacted with lactic acid produced ester compound (1), then the carboxylic acid of lactic acid could reacted with free Procain oil produced amide attachment, the controlled drug release in different pH values at 37C˚was studied to improve their characteristic and to minimize the side effect of the drug could be used in broad spectrum activity as atherapeutic material.This mutual prodrug was used with another biological active drug instead of single action. The prepared prodrug was charac

Small molecules drug conjugate mutual prodrug design  (SMDC) composed of folate and lethal agent conjugate, rigidly bonded via hydrophilic bridge and self immolative disulfide  bond   ;  represent new interesting approaches for cancer treatment , the component of SMDC intended  for targeting    folate receptor , along with greater conservation  of component until reaching  the target tumor tissue . The  designing and synthesis of compound VI and VIII derived from 6-Mercaptopurine (6-MP) and Methotrexate ( MTX) conjugate altogether as mutual prodrugs were  processed forward  successfully by multistep reaction  procedures , and by Thin Layer Chromatography (TLC) for

The purpose of this research work is to synthesize conjugates of NSAIDs (ibuprofen, and naproxen) with sulfadiazine as possible mutual prodrugs to overcome the local gastric irritation of NSAIDs with free carboxyl group by formation of ester linkage that supposed to remain intact in stomach and may hydrolyze in intestine chemically or enzymatically; in addition to that attempting to target the synthesized derivative to the colon by formation of azo bond that undergo reduction only by colonic bacterial azoreductaze enzyme to liberate the parent compound to act locally (treatment of inflammation and infections in colon)

As possible mutual prodrug had been synthesized that contain metronidazole and dexamethazone conjugated through phosphodiester linkage. The rationale for this type of conjugate is to get a prodrug with possible site – specific delivery of its active constituents into the lower parts of the G.I.T.

This compound was synthesized by the reaction of dexamethzone – 21 – phosphate with metronidazole to form:(1 – (dexamethazone – 21 – phosphoryl) – metronidazole)

   This conjugate was performed using dicyclohexylcarbodiimide (DCC) as a condensing agent. The identity of the prepared compound had been confirmed using T.L.C., U.V. spectroscopy, IR spectrosco

The purpose of this research work is to synthesize conjugates of some NSAIDs with sulfamethoxazole as possible mutual prodrugs to overcome the local gastric irritation of NSAID with free carboxyl group by formation of ester linkage that supposed to remain intact in stomach and may hydrolyze in intestine chemically or enzymatically; in addition to that attempting to target the synthesized derivative to the colon by formation of azo group that undergo reduction only by colonic bacterial azo reductaze enzyme to liberate the parent compound to act locally (treatment of  inflammation and infections in colon).

Key words: Mutual prodrug, Ester linkage, Azo bond, Colon targeting

The purpose of this research work is to synthesize conjugates of some NSAIDs with sulfamethoxazole as possible mutual prodrugs to overcome the local gastric irritation of NSAID with free carboxyl group by formation of ester linkage that supposed to remain intact in stomach and may hydrolyze in intestine chemically or enzymatically; in addition to that attempting to target the synthesized derivative to the colon by formation of azo group that undergo reduction only by colonic bacterial azo reductaze enzyme to liberate the parent compound to act locally (treatment of inflammation and infections in colon)