INTRODUCTION:

Sulfur compounds are a class of chemical compounds that contain the (S-R , S-Cycle) group , it is present in many of the chemical compounds, so sulpho group are very important to prepare a wide range of medical compound⁽¹⁾, and got a special importance in the pharmaceutical industry because play an active role in biological system and macro bio molecules²⁾. Some of them are used to treat different diseases like medicine and pharmaceutical field of the thyroid gland and thyroid leukemia⁽³⁾, Effective in stimulating the heart and lungs work⁽⁴⁾, Effective against breast cancers⁽⁵⁾, and sulpho compound showed biological active towards microbial represented by bacteria and fungi ⁽⁶⁾, types of viruses⁽⁷⁾, Effective towards bacteria Staphylococcus aureus and E. coli⁽⁸⁾.,sulfur are pervasive in nature and technology as structural materials. The sulfur compounds linkage are easily formed, confers structural rigidity, and resists hydrolysis. Sulfur drugs like :

Fig(1) : Sulfur compounds as drugs

Organo sulfur compounds are organic compounds that contain sulfur. They are often associated with foul odors, but many of the sweetest compounds known are organosulfur derivatives, e.g., saccharin. Nature abounds with organosulfur compounds—sulfur is essential for life. Of the 20 common amino acids, two (cysteine and methionine) are organosulfur compounds, and the antibiotics penicillin (pictured below) and sulfa drugs both contain sulfur. While sulfur-containing antibiotics save many lives, sulfur mustard is a deadly chemical warfare agent. Fossil fuels, coal, petroleum, and natural gas, which are derived from ancient organisms, necessarily contain organosulfur compounds, the removal of which is a major focus of oil refineries^(12-18).

Fig(2) : Sulfur compound as antibacterial - Penicillin

Variety of sulfur containing scaffolds widely exists in natural products and drugs.

These compounds are characterized by C−S−C bondsRelative to C−C bonds, C−S bond are both longer, because S is larger than carbon, and about 10% weaker^(19-26). Representative bond lengths in sulphur derivatives are 183 pm for the sulfur – carbon (S−C ) single bond in methane thiol and 173 pm in thiophene. The carbon - sulfur (C−S)bond dissociation energy for thio methane is 89 kcal/mol (370 kJ/mol) compared to methane's 100 kcal/mol (420 kJ/mol) and when hydrogen atom is replaced by (CH₃) group the energy decreases to 73 kcal/mol (305 kJ/mol). The single carbon to oxygen bond is shorter than that of the C−C bond. The bond dissociation energies for di alkyl sulfide and dimethyl ether are respectively 73 and 77 kcal/mol (305 and 322 kJ/mol) ^{(27 -41)}.

EXPERIMENTAL AND MATERIALS:

All chemicals and instrumentals carried out in college of education, biological studying carried out in Bio – lab in biological department., Chemical Studying carried out in chemistry department .

EXPERIMENTAL PROCEDURES:

The biological activities of synthesized compounds have been studied for their antibacterial activities by agar via biological methods⁽¹⁶⁾ . The antibacterial activities were done at (0.001 M) concentrations in (DMSO) solvent through using two types of bacteria ( Staphylococcus aureu and Salmonella typhi). These bacterial strains were incubated for 24 hr at 37^oC.

Synthesized Compounds In Schemes:

In our schemes , we synthesized compounds , but now we will study the biological activity for them in this work :

RESULTS AND DISCUSSION:

The synthesized compounds screened for Biological Activity against two types of bacteria .

Biological Tests:^{(16 ,19)}

The test of the sensitivity of the bacteria , which included work on two types of bacteria to measure the biological activity of certain compounds which bacteria positive for the dye Cram (bacteria Staphylococcus aureu) and negative gram (bacteria Salmonella typhi), and Table (1) shows the diameter of inhibition zone for vehicles chemical measured in mm towards the bacteria.

Table 1: Biological Activity (Inhibition Zone in (mm)) of Compounds[1 - 4] in Concentration (0.001 M).

Comp. No.	( G +) *Staphylococcusaureus*	( G - ) *Salmonellatyphi*
[1]	10	6
[2]	20	16
[3]	4	--
[4]	16	10

The results showed the Biological Activity for compounds (2, 4) the effectiveness of anti-resistant bacteria is much higher than other compounds in the inhibition of bacteria, thiadiazepine cycle and thiazine, which gave vital to the effectiveness of many of the bacteria, and the following photos show the following:

Picture (1).The amount of inhibition of the compounds on Staphylococcus aureu

Picture (2).The amount of inhibition of the compounds on Salmonella typhi

Chromatography Behavior of Compounds :

Solutions of compounds were prepared in concentration (1 ppm), and injected by using a syringe (Hamilton ) in capacity (10ml) through nitrogen (gas flow 25 ml/min) . The compounds separated according to polarity and molecular weight ., for this reason , compound [3] separated in the first time due to⁽²¹⁾ its polarity (presence of OH group in structure and NH group), then compounds [1] and [2] , then compound [4] , because of their high molecular weight more than other compounds , figures (3-6).

Fig (3): Chromotogram of Compound [ 1 ]

Fig ( 4): Chromotogram of Compound [ 2 ]

Fig (5): Chromotogram of Compound [ 3 ]

Fig (6): Chromotogram of Compound [ 4 ]

REFERENCES:

1. PA Insel. Analgesic-antipyretic and anti-inflammatory agents and drugs employed in the treatment of gout. In: JG Hardman, LE Limbird, PB Molinoff, RW Ruddon, GA Gilman. The pharmacological Basics of Therapeutics, 9th edition. McGraw Hill, New York, 1996, 617-657.

2. N. Bramhananda Reddy, VenkataramuduBurra, L. K. Ravindranath, S. A. Aleemand N. S. Narendra, Der Pharma Chemica, 8(4):101-112,101-112, 2016.

3. Subbiah Ramasamy, Tanmoy Guria, Tanushree Singha, Puspita Roy, Benu P Sahu, Jayatri Naskar, Avijit Das and Tapan K Maity., Der Pharma Chemica,8,4,446-452, 2016.

4. Sahar Balkat Aljuboorya and Ammar A. Razzak Mahmood Kubba., Der Pharma Chemica, 8,4, 63-66.63-66, 2016.

5. Y. Filali Baba, H. Elmsellem, Y. Kandri Rodi, H. Steli, C. AD5, Y. Ouzidan,F. OuazzaniChahdi, N. K. Sebbar, E. M. Essassi and B. Hammouti., Der Pharma Chemica, 8,4,159-169, 2016.

6. Kiran M. Kulkarni, Sagar A. Jadhav, Pramod B. Patil, Vikas R. Dholeand Shitalkumar S. Patil, Der Pharma Chemica, 8,4,1-5, 2016.

7. Chao jun-shu, Huia ping-xin, Lia shuo, “Synthesis and Antibacterial Activities of Novel Biphenyltetrazole Derivatives Bearing 1,3,4- Oxadiazole.” Journal of the Chinese Chemical Society, 2005, 52, 539-544 539.

8. Srinivas K, Srinivas U, Bhanuprakash K, Harakishore K. "Synthesis and antibacterial activity of various substituted s-triazines". Eur J Med Chem 2006; 41: 1240-1246.

9. KD Tripathi. Essentials of medical pharmacology. Jaypee Brothers Medical Publishers Ltd, New Delhi, India, 2008, 189.

10. Aatesh Èznur, Kocabalkanli AysËe, Cesur Nesrin, “Synthesis and antimicrobial activity of some 5-aryl-2-[(N,N-disubstituted thiocarbamoylthio) acylamino]-1,3,4-oxadiazoles” , Farmaco , 53 (1998) 541-544.

11. Montalbetti, Christian A. G. N.; Falque, Virginie, (2005). "Amide bond formation and peptide coupling". Tetrahedron. 61 (46): 10827–10852., doi:10.1016/j.tet. 2005.08.031

12. Valeur, Eric; Bradley, Mark (2009). "Amide bond formation: beyond the myth of coupling reagents". Chem. Soc. Rev., 38: 606–631. doi:10.1039/ B 701677H.

13. Nanjunda S, Swamy S, Basppa, Priya Bs, Prabhuswamy B, Doreswamy BH (2006). "Crystal Structure of Novel 2-butyl-4-chloro-1HImidazolyl-5-Carboxaldehyde" . European Journal. of Medicinal Chemistry ,41: 531-538.3.

14. Jin, Jiang Chen, Baoan Song, Zhuo Chen, Song Yang, “Synthesis, structure, and bioactivity of N0-substituted benzylidene - 3,4,5-Trimethoxybenzo hydrazide and - acetyl-2-substituted phenyl-5-(3,4,5-trimethoxyphenyl)-2,3-dihydro-1,3,4-oxadiazole derivatives.”, Bioorganic and Medicinal Chemistry Letters 16 (2006) 5036–504.

15. Aboraia S. Ahmed, Rahman-abdel.M hamdy, Mahouz M. nadia, “Novel 5-(2 hydroxyphenyl)-3-substituted-2,3-dihydro-1,3,4-oxadiazole-2-thione derivatives: Promising anticancer agents.” Bioorganic and Medicinal Chemistry 14 (2006) 1236–1246.

16. Nagham Mahmood Aljamali., " Synthesis of Antifungal Chemical Compounds from Fluconazole with (Pharma- Chemical) Studying" ., Research journal of Pharmaceutical, biological and chemical sciences., 8 (3)., p. 564 -573 , 2017 .

17. Nagham Mahmood Aljamali, "Synthesis and Biological Study of Hetero (Atoms and Cycles) Compounds", Der Pharma Chemica, 2016, 8(6):40-48.

18. B. J. Hathaway and D. E. Billing, “The electronic properties and stereo chemistry of mono-nuclear complexes of the copper(II) ion,” Coordination Chemistry Reviews, vol. 5, no. 2, pp. 143–207, 1970.

19. R. V. Singh, R. Dwivedi, and S. C. Joshi, “Synthetic, magnetic, spectral, antimicrobial and antifertility studies of dioxo molybdenum(VI) unsymmetrical imine complexes having a 𝑁=𝑁 donor system,” Transition Metal Chemistry, vol. 29, no. 1, pp. 70– 74, 2004.

20. Nagham Mahmood Aljamali , Intisar O , "Synthesis of Sulfur Heterocyclic Compounds and Study of Expected Biological Activity" , Research J. Pharm. and Tech. ,2015, 8(9) ,1225-1242 .,DOI: 10.5958/0974-360X.2015.00224.3.

21. Nagham M Aljamali , Saher M, Zainab M, Seena K. , "Microbial Studying of (Thiazole ,Oxadiazole, Thiadiazole)–Derivatives on Mouth and Teeth Bacteria ", International Journal of Medical Research and Pharmaceutical Sciences, 2016, 3, 8 ,30-39 , DOI:10.5281/zenodo.61357 .

22. Nagham .M .Aljamali , "Methods of preparation and identification of various membered ring ", 1th Ed., Alnoor publishing , Germany , (2017).

23. H. Nozaki; H. Takaya; S. Moriuti; R. Noyori (1968). "Homogeneous catalysis in the decomposition of diazo compounds by copper chelates: Asymmetric carbenoid reactions". Tetrahedron. 24 (9): 3655–3669. , doi:10.1016/S0040-4020(01)91998-2.

24. J.C. Hindson; B. Ulgut; R.H. Friend; N.C. Greenham; B. Norder; A. Kotlewskic; T.J. Dingemans (2010). "All-aromatic liquid crystal triphenylamine-based poly(azomethine)s as hole transport materials for opto-electronic applications". J. Mater. Chem. 20 (5): 937–944., doi:10.1039/B919159C.

25. Cremlyn, R. J. (1996). An Introduction to Organosulfur Chemistry. Chichester: John Wiley and Sons. ISBN 0-471-95512-4.

26. García Ruano, J. L.; Cid, M. B.; Martín Castro, A. M.; Alemán, J. (2008). "Acyclic S,S-Dialkylsulfimides". In Kambe, N. Science of Synthesis. 39. Thieme. pp. 352–375. ISBN 978-1-58890-530-7.

27. Drabowicz, J.; Lewkowski, J.; Kudelska, W.; Girek, T. (2008). "S,S-Dialkyl sulfoximides". In Kambe, N. Science of Synthesis. 39. Thieme. pp. 154–173. ISBN 978-1-58890-530-7.

28. Drabowicz, J.; Lewkowski, J.; Kudelska, W.; Girek, T. (2008). "S,S-Dialkyl sulfonediimines". In Kambe, N. Science of Synthesis. 39. Thieme. pp. 173–180. ISBN 978-1-58890-530-7.

29. Zhang, Y.; Hogg, N. (2005). "S-Nitrosothiols: cellular formation and transport". Free Radical Biol. Med. 38 (7): 831–838. doi:10.1016/ j.freeradbiomed. 2004.12.016. PMID 15749378.

30. Braverman, S.; Cherkinsky, M.; Levinger, S. (2008). "Alkylsulfur Trihalides". In Kambe, N. Science of Synthesis. 39. Thieme. pp. 187–188. ISBN 978-1-58890-530-7.

31. Sheppard, W. A. (1962). "Arylsulfur Pentafluorides". J. Am. Chem. Soc. 84: 3064–3072. doi:10.1021/ja00875a006.

32. Drabowicz, J.; Lewkowski, J.; Kudelska, W.; Girek, T. (2008). "Dialkylsulfur Tetrahalides". In Kambe, N. Science of Synthesis. 39. Thieme. pp. 123–124. ISBN 978-1-58890-530-7.

33. Moltzen, E. K.; Klabunde, K. J.; Senning, A. (1988). "Carbon monosulfide: a review". Chem. Rev. 88 (2): 391. doi:10.1021/cr00084a003.

34. Pötter, B.; Seppelt, K. (1984). "Trifluoroethylidynesulfur Trifluoride, F3C−C≡SF3" . Angew. Chem. Int. Ed. Engl. 23 (2): 150. doi:10.1002/anie.198401501.

35. Nagham Mahmood Aljamali and Dhuha Rahi .,"New Formazan Compounds (Synthesis, Identification, Physical Properties)"., Journal of Chemical and Pharmaceutical Sciences ,Volume 10 Issue 3, 2017 .

36. Nagham Mahmood Aljamali and Ahmed Adnan Abdul Hussein ., "Antibacterial Studying Of Some New Various Mannich Base Derivatives" , J.Bio.Innov 6(1), pp: 91- 99, 2017 .

S. Sreedaran, K. S. Bharathi, A. K. Rahiman et al., “Synthesis, electrochemical, catalytic and antimicrobial activities of novel unsymmetrical macrocyclic dicompartmental binuclear nickel(II) complexes,” Polyhedron, vol. 27, no. 7, pp. 1867–1874, 2008.

37. Nagham Mahmood Aljamali ., " Synthesis And Chemical Study Of New Sulfone Compounds" ., Int. J. Curr.Res.Chem.Pharma.Sci. 1(9): (2014):78–87 .

38. Nagham Mahmood Aljamali .," Review in Azo Compounds and its Biological Activity " ., Biochem Anal Biochem 2015, 4:2 ., http://dx.doi.org/10.4172/2161-1009.1000169.

39. Nakamoto, N. Infrared and Raman Spectra of Inorganic and Coordination Compounds, 6thEd, Part 2 John Wiley and Sons, Inc., New Jersy, 2009.

40. Saher Mahmood Jwad ., Research Journal of Pharmaceutical, Biological and Chemical Sciences ., 8, 3, 2017, 549 –563.

Received on 23.05.2017 Modified on 17.06.2017

Asian J. Research Chem. 2017; 10(4):526-530.

DOI:10.5958/0974-4150.2017.00087.6