doi.org/10.36721/PJPS.2020.33.5.REG.2067-2081.1 Pak. J. Pharm. Sci., Vol.33, No.5, September 2020, pp.2067-2081 2067 Dithiin diisoimides: Synthesis and their antimicrobial studies Sumbul Ahmed 1 , Shahnaz Perveen 1,2 *, Khalid Mohammed Khan 2,5 , Farzana Naz 2 , Rahat Azher Ali 3 , Munazza Ajaz 4 and Samreen Shah 4 1 PCSIR, Laboratories Complex, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi-75280, Pakistan 2 H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi- 75270, Pakistan 3 Department of Chemistry, University of Karachi, Karachi-75270, Pakistan 4 Department of Chemistry, Federal Urdu University for Arts, Science and Technology, University Road, Gulshan-e-Iqbal Campus, Karachi, Pakistan 5 Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia Abstract: Sixteen derivatives of dithiin diisoimide 2a-2p have been synthesized and screened for antibacterial and antifungal activity. Compounds 2a-2g and 2i-2p are almost same or more active than gentamicine against Acinetobacter. Whereby compound 2,6-didodecyl-1H,5H-pyrrolo[3',4',5,6][1,4]dithiino[2,3-c]pyrrole-1,3,5,7(2H,6H)-tetrone (2d) having zone of inhibition 20 mm against Acinetobacter is the most potent among all these compounds and can be used as lead compound for the treatment of Acinetobacter infection. Keywor ds : Dithiin diisoimides, succinamic acid, succinamic anhydride, amines, antibacterial INTRODUCTION Dithiins are included in phyto chemicals assist to maintain good health, lowers the cholesterol and triglyceride level and high blood pressure, results secure cardiovascular health. It helps to fight with diseases caused by infection and also effective against certain types of cancer. Garlic contains sulfur, and sulfur is itself an element that showed antioxidant activity. It is useful as an antiseptic, poor digestion and cough (Corzo-Martinez et. al ., 2007). 2- Vinyl-4H-1,3-dithiin present in garlic, it act as antithrombotic and platelet aggregation inhibitory activity (Corzo-Martinez et al ., 2007). The recent research revealed that there are a number of sulfur containing organic compounds are found in garlic (Allium sativom Linn) which are responsible for its activity. These compounds, include allin (an allicin precursor), allicin, ajoene, scordinin, dithiins and diallyl sulfides (Bruno et. al ., 2009; Kim, et. al ., 1995). Allicin, have antibiotic and antithrombogenic activities. It has been also found that garlic will preserve its activity if it is processed in a way which keep its sulfur compounds from degradation by stomach acids. From centuries it has been used for the treatment of asthama, respiratory ailments, diabetes, pneumonia, rheumatism and cardiovascular disorder etc. The typical aroma of freshly chopped of the genus Allium is due to dithiin (which have two sulfur atoms), it is found in traces. It is detected by using cryogenic techniques GC-MS and HPLC (Abu-lafi et al ., 2004). Dithiins contain divalent sulfur and are six-member heterocyclic cyclacene (Kornmayer et al ., 2009; Finar et al ., 2007). 1,4-Dithiin ring is non-planar and angle linking C-S-C is 137 ° . Dicoordinated sulfur undergoes ring inversion and calculated energy barrier to ring inversion (4↔5) is 6.4 Kcal/mol [fig. 1] (Moriarty et. al ., 1973). Dithiin diisoimide possesses dithiin 3 moiety which has redox potential and capable to generates stable radical cations. Thermally stable dithiin undergoes oxidation reaction with H 2 O 2 to form mono or disulfone (Andreu et. al ., 2001). Compounds having 1,4-dithiin moiety have an ability to donate electrons so it can easily undergo isomerization, i.e. 1,4,5,8-tetrathianaphthlene TTN isomerizes into tetrathiafulvalene TTF. Sulfur could be removed from dithiin that lead to the formation of cis configurated double bonds (Caputo et al ., 1994). Dithiin diisoimide proved to be very important biologically active molecule. Dithiin diisoimide and succinamic acid derivatives can be prepared by many ways (Amelichev et al ., 2006; Safavy et al ., 1997; MacDonald et al ., 1980; Tarko et al ., 2006; Geo et al ., 1964; Itagaki et al ., 2003; Kunkel, and Holstad, 1996; Burdulene et al ., 1999; Arrizabalaga et al ., 1984; Rankin et. al ., 2001; Huang, and Risley, 2000; Finar et al ., 2007; Cesare et al ., 2004; Parham et al ., 1959; Yamamoto et al ., 2004; Murru et al ., 2007; Zaidi et al ., 2006). As dithiins have significant biological activity, therefore, we decided to synthesize the libraries of dithiin diisoimides derivatives with different substitution at nitrogen with aliphatic and aromatic groups in order to get an active compound which may act as lead molecule for antibacterial. Therefore, in search of potent biologically active compounds, we have synthesized sixteen dithiin diisoimide derivatives 2a-2p and evaluated their *Corresponding author: e-mail: dr_shahnaz_perveen@yahoo.com