ناقش قسم الكيمياء في كلية التربية للعلوم الصرفة (ابن الهيثم) رسالة الماجستير الموسومة (تحضـــير ودراســــة الفعـــالية البيولوجية لمركـــبات حلقيـــة غير متجانسة جديـــدة مشـــتقة مـــن مشـــتقات الهــايدرازايد) للطالبة (وسن مجيد عبد الحميد عبد الله) التي انجزتها تحت اشراف تدريسيتا القسم (أ.د. جمبد هرمز توما و أ. م. رجـــاء كاظــم باقـــر) ونوقشت من قبل أعضاء لجنة المناقشة المبينة أسمائهم فيما يأتي:

  • أ. د. اسامة سلمان عبد الرزاق (رئيسا)

  • أ. د. نسرين حسين كرم (عضوا)

  • أ. م. نورهان خالد شفيق (عضوا)

  • أ.د. جمبد هرمز توما (عضوا و مشرفا)

  • أ. م. رجـــاء كاظــم باقـــر (عضوا و مشرفا)

يتضمن هذا البحث تحضير وتشخيص ودراسة النشاط البيولوجي للمركبات الحلقية الغير المتجانسة الجديدة المشتقة من مركبات الهيدرازيد .

تم تحضير مشتقات 4,2,1-تريازول-3-ثيول و الإستر والهيدرازيد المشتقة منه وذلك من خلال تفاعل غلق الحلقة لمركبات هيدرازين كاربوثيو أميد a[IV] و b[IV] في  ٪ 4 من هيدروكسيد الصوديوم  حيث نتج عنه تكوين 4,2,1- تريازول a,b[[V، ومن ثم مفاعلت الاخير مع اثيل كلورو اسيتيت بوجود خلات الصوديوم المنصهرة والايثانول  لينتج مركب الاستر a,b[VI]. ومن تكاثف مركب االاستر  مع الهيدرازين٪ 80 حصلنا على  مركبات هيدرازيد جديدة  a,b[VII] والتي تمت مفاعلتها في مسارين :

  •   يتضمن المسار الأول تحضير مشتقات حامض الأميك [IX]a,b، [VIII]a,bمن تفاعل المركب ,b  [VII]a مع أنهدريد حامض الفثاليك أو النفثاليك في الاسيتون كمذيب.

  • بينما يتضمن المسار الثاني تحضير 4,3,1-أوكساديازول a,b[X] بدءًا من تفاعل حامض الهيدرازيد a,b[VII] مع حامض 4-أمينوبنزويك باستخدام  POCl3عن طريق تفاعل غلق  الحلقة. استخدم مركب الاوكسادايازول المحضر في تحضير قواعد شف واميدات جديدة وذلك من  تفاعل مركبات الاوكساديازول المحضرة مع الديهايدات متنوعة في الايثانول لينتج قواعد شف [XI] a-d , [XII] a-d اما تفاعله مع كلوريد الحامض بوجود مزيج من (py , DMF)  بدرجة (5-10) درجة مئوية اعطى اميدات جديدة  [XIV] a-e [XIII] a-e,.

  • شخصت جميع المركبات المحضرة اعلاه بواسطة اطياف الاشعة تحت الحمراء وطيف الرنين النووي المغناطيسي 1HNMR وطيف الكتلة (للبعض منها).

  • درست الفعالية البيولوجية لبعض من المركبات المحضرة باستخدام ثلاثة انواع من بكتريا؛ Bacillus subtilis , staphylococcus aureus gram positive وcoli  gram negative ومن الفطريات نوع واحد candida tropicalis . اظهرت المركبات المدروسة فعالية جيدة الى متوسطة تجاه البكتريا من نوع كرام موجب) عند تركيز (10-2 ولم يعطي اي فعالية بيولوجية تجاه البكتريا من نوع كرام سالب. بالإضافة الى ذلك درس نشاط الإنزيمات لهذه المركبات GOT و GPT و ALP واليوريا والكرياتينين ولأجل تأكد من سلامة المركبات المحضرة تم اجراء فحص سمية لها اولا.

Synthesis and Study the Biological Activity of New Heterocyclic Compounds Derived from Hydrazide Derivatives

Wasan Majeed Abd Al-Hameed  

Prof. Dr. Jumbad Hermiz Tomma     and Ass. Prof. Rajaa Kadhium Baker

The aim of the work   

       Heterocyclic compounds are importance for biochemical processes due to their different applications, especially in the field of chemotherapy antimicrobials, pesticides, agriculture and fungicides. The current study was directed to the synthesis of new heterocyclic compounds derived from hydrazide derivatives and study some of their biological activity and enzymes activity as shown in the following steps: –

Synthesis and characterization of new heterocyclic compounds are derived from 5, 6-diphenyl-1, 2, 4-triazine-3-thiol as follows:

Preparation of ester compounds and their acid hydrazides, and using the later compounds in synthesis of 3-thiol-1, 2, 4-triazoles.

Synthesis and characterization of ester and their acid hydrazide (are derived from the synthesized 3-thiol-1, 2, 4-triazoles). This acid hydrazide was converted to amic acid derivatives and 1, 3, 4-oxadiazole compounds (containing amino group).

Synthesis and characterization of new Schiff bases and amides (are derived from the synthesized 1, 3, 4-oxadiazole compounds).

Study the biological activity (antibacterial and antifungal) for some of different type of the heterocyclic synthesized compounds.

Study the toxicity and enzymes activity of some of different type of heterocyclic synthesized compounds.

  

  Abstract

        The work involves synthesis, characterization and study the biological activity of new heterocyclic compounds derived from hydrazide derivatives and this work can be summarized by the following, Scheme I and II:

         The synthesis of 1,2,4-triazole-3-thiol derivatives, their ester and hydrazide via  a cyclization reaction  of  the  hydrazine carbothioamide compounds [IV]a and [IV]b in  4% NaOH to formation 1,2,4-triazoles [V]a,b, which were refluxed with ethyl chloro acetate in ethanol and sodium acetate to give ester compounds [VI]a,b. Condensation of ester-compounds [VI]a,b with hydrazine hydrate 80% led to formation new hydrazide compounds [VII]a,b which were reacted in two routes:

        The first synthetic route involve synthesis of amic acid derivatives [VIII]a,b –[IX]a,b from the reaction of hydrazide compounds [VII]a,b with phthalic or naphthalic acid anhydride. The second route involve synthesis of 1,3,4-oxadiazoles [X]a,b by closing the ring reaction of acid hydrazide [VII]a,b, with 4-aminbenzoic acid in POCl3. Finally the compounds [X]a,b  was reacted with aromatic substituted aldehydes in ethanol to get Schiff bases compounds [XI]a-d, [XII]a-d, while when reacted with acide chloride in (py , DMF) at (5-10 ºC) led to from new amides [XIII]a-e, [XIV]a-e.

        All the synthesized compounds were characterized by FTIR, 1HNMR and mass spectrometer (some of them).

   Most of new synthesized compounds were tested against antibacterial activity; Bacillus subtilties, staphylococcus aureus gram positive and E. coli gram negative bacteria and also candida tropicalis as fungal. The examined compounds showed a good moderate antimicrobial activity towards (G + at concentration 10-2) and did not show any biological activities towards (G -). To ensure the safety of the synthesis compounds the toxicity were examined. Some of new synthesized compounds were tested by enzymes activity; GOT, GPT, ALP and urea, creatinine.

Conclusions

        In this work new derivatives include triazoles, their esters with their hydrazides and amic acids besides to oxadiazole derivatives were synthesized and characterized, As shown in the following sentences:

The compounds [V]a,b was synthesized by the cyclization of hydrazine carbothioamide compound [IV]a,b in a solution of 4% NaOH  at long time and good yields the compounds;1,2,4-triazole-3-thiol were used as starting material for synthesis of new derivatives esters [VI]a,b and hydrazide [VII]a,b in good yield by simple methods.

Amic acids compounds [VIII]a,b-[IX]a,b were synthesized by the reaction of

Phthalic or naphthalic anhydride with hydrazide compound [VII]a,b in acetone at room temperature in good yield .

New 1,3,4-oxadiazole compounds [X]a,b were synthesized by the reaction of acid hydrazide [VII]a,b with 4-aminobenzoic acid in the presence of (POCl3) in moderate yields, these oxadizoles were used as a starting material for synthesis of new Schiff bases [XI]a-d,[XII]a-d in low yields and synthesis of new amides compounds [XIII]a-e, [XIV]a-e in good yields at short time.

The physical properties and spectral data gave a good information and indicated the suggested structure for the new synthesized compounds.

The synthesized compounds which were examined against three type of bacteria provided good to moderate biological activity towards gram positive (G+ at concentration 10-2) and not shown any biological activity towards (G-). This may be related to the presence of the functional groups and the type of heterocyclic units.

The obtained results of this study showed: Firstly, the possibility of using the prepared compounds which has biological effect was studied as antibiotics, especially compound [V]a and compound [VIII]b. Secondly, the possibility of using these compounds as preservatives, especially after it was proven that they are not toxic and have no effect on liver enzymes. The first indicator of any harm to the body.

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كلية التربية للعلوم الصرفة (ابن الهيثم) College of Education for Pure Science (Ibn Al-Haitham)

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