Evaluation of DNA Binding with Some Sele cted Hydrazide and Semicarbaz ide De rivati ves

Evaluation of DNA Binding with Some Selected Hydrazideand Semicarbazide Derivatives

Sannapaneni Janardan & Pothini Suman & G. Swapna &

A. Amrita & R. Priya & Ramamoorthy Siva &

Kari Vijayakrishna & Akella Sivaramakrishna

Received: 31 August 2013 /Accepted: 20 March 2014 /Published online: 11 April 2014# Springer Science+Business Media New York 2014

Abstract A group of hydrazide and semicarbazide derivatives containing isopropylidene,benzylidene, cyclohexylidene, and phospholidene groups was synthesized and characterizedby spectroscopic techniques. These compounds were tested for DNA interaction studiesmonitored by UV-Vis and IR data as well as molecular docking. Investigations on interactionsof these compounds with DNA revealed an intercalative mode of binding between them. It isinteresting to note that semicarbazide derivatives with aliphatic substituents showed betterDNA binding than the aromatic substituents.

Keywords Hydrazide and semicarbazide derivatives . Synthesis . Structural characterization .

DNA binding study

Introduction

Hydrazine is generally known as a powerful reducing agent, and research on the synthesis ofhydrazide-, semicarbazide-, and thiosemicarbazide-based molecules possessing azomethine“NHN=CH” is gaining a lot of significance due to their unusual medicinal properties [1–5].They are capable of acting as neutral or charged ligand moieties, as they have interestingcoordination properties because only the β-nitrogen coordinates to the metal atom, while theα-nitrogen atom remains uncoordinated [6–8].Moreover, the coordination chemistry of transitionmetals with hydrazide and semicarbazides as ligands from the hydrazide family is of great interestdue to different bonding modes with both electron-rich and electron-poor metals [6–10]. There-fore, many researchers have synthesized these compounds as target structures and evaluated theirbiological activities. Acid hydrazides have recently been investigated for testing their potentialityas tuberculostats [11–17]. Hydrazides and their condensation products have displayed diverse

Appl Biochem Biotechnol (2014) 173:596–608DOI 10.1007/s12010-014-0868-4

S. Janardan : P. Suman : G. Swapna :K. Vijayakrishna :A. Sivaramakrishna (*)Department of Chemistry, School of Advanced Sciences, VIT University, Vellore 632 014 Tamil Nadu, Indiae-mail: [email protected]

A. Amrita : R. Priya : R. SivaPlant Biotechnology Division, School of Bio Sciences and Technology, VIT University, Vellore 632 014,India

range of biological properties such as bactericidal [18], antifungal [19], anticonvulsant [20],antihelmintic [21], antitumor [22, 23], antileprotic [24], antimalarial [25], anticancer [26],antidepressant [27], anti-HIV [28], analgesic-anti-inflammatory [29], leishmanicidal [30], andvasodilator activities [31]. In addition to this, a series of 6,8-dibromo quinazolin-4(3H)-one-basedsemicarbazides and their corresponding Schiff base derivatives [32] and their coordinationbehavior [33] has been reported. Conversion of semicarbazides to the correspondingoxadiazolinones has been discussed [34]. Some of these semicarbazides were used in thepreparation of lanthanummanganite nanopowders through the solution combustion method [35].

The interaction of small molecules with DNA plays an imperative role in many biologicalprocesses [36]. As DNA is often the target for majority of anticancer and antibiotic drugs, studieson the interaction of drug and DNA have a key role in pharmacology [37, 38]. Moreover,understanding the interactions of small molecules with DNA is of prime significance in the rationaldesign of more powerful and selective anticancer agents [39]. The intercalative binding propertiesof such molecules can also be harnessed as diagnostic probes for DNA structure in addition toDNA-directed therapeutics [40]. These aspects prompted us to focus on the hitherto unknownDNA interaction studies of some selected hydrazide and semicarbazide derivatives (Fig. 1).

Experimental Work

Materials

The chemicals such as nicotinic hydrazide, 1,2-bis(diphenylphospheno)ethane, bromine,triethylamine, t-butyl phenylhydrazide, cyclohexanone, and triphenylphosphine were

Fig. 1 Molecules utilized in the present work

Appl Biochem Biotechnol (2014) 173:596–608 597

purchased from Sigma-Aldrich and used as such without further purification. Benzaldehyde,sodium acetate, carbon tetrachloride, methanol, acetone, and chloroform were purified bystandard procedures.

Instrumentation

1H NMR and 13C NMR spectra were determined in CDCl3 and DMSO-d6 solutions at400 MHz using the Bruker Ascend model. Fourier transform infrared (FT-IR) spectra wererecorded on a Shimadzu IRAffinity-1 spectrophotometer. UV-Vis spectra were recorded on aSYSTRONICS AU-2701 UV-Vis spectrophotometer. Mass spectra were recorded on aPerkinElmer Clarus 680 (GC) and Clarus 600 (EI, mass). The acquisition parameters are asfollows: oven initial temperature 60 °C for 2 min, ramp 10 °C/min to 300 °C, hold 6 min, totalrun time 32.00 min, InjAuto = 250 °C, volume = 1 μL, split = 10:1, flow rate 1 mL/min, carriergas = He, and column = Elite-5MS (30.0 m, 0.25 mm ID, 250 μm df). For mass condition (EI),the following parameters are used: solvent delay = 2.00 min, transfer temperature = 230 °C,source temperature = 230 °C, and scan 50 to 600 Da.

Experimental Procedures

2-(Propan-2-ylidene)hydrazinecarboxamide (1) To 0.5 g (6.66 mmol) of semicarbazide hy-drochloride salt, 1.04 g (18.0 mmol) of sodium acetate was added and the mixture wasdissolved in 1.32 mL (18.0 mmol) of acetone and stirred for 2 h. The obtained white precipitatewas washed with cold ethanol and diethyl ether and then dried under high vacuum for 2 h.Yield 0.48 g (84 %); m.p. 186–187 °C; IR (KBr, cm−1): ν 3,642.22 (NH), 3,263 (NH2), 2,914(C–H), 1,687.71 (C = O); 1H NMR (D2O, 400 MHz): δ 9.07 (s, 1H, NH), 6.278 (s, 2H, NH2),1.797 (s, 3H, CH3), 1.876 (s, 3H, CH3);

13C NMR (400 MHz): δ 159.76 (C = O), 146.76(N = C), 24.67 (CH3), 16.88 (CH3); MS (ESI): 115.23 (M+).

N′-(Propan-2-yilidene)nicotinohydrazide (2) To 0.5 g (3.6 mmol) of nicotinic hydrazide,1.83 mL (18 mmol) of acetone was added and stirred for 2 h at room temperature. A whitecrystalline solid was obtained. This precipitate was washed with cold ethanol and diethyl etherand then dried under high vacuum for 2 h. Yield 0.45 g (84 %); m.p. 186–187 °C; IR (KBr,cm−1): ν 3,441.01 (NH), 3,008.95 (C–H), 1,649.14 (C = O),; 1H NMR (CDCl3, 400 MHz): δ9.27 (s, 1H, NH), 7–9 (m, 4H), 2.023 (s, 3H, CH3), 1.906 (s, 3H, CH3);

13C NMR: δ 166.46(C = O), 162.41 (N = C), 122.72–148.14 (Ph), 17.23, 25.48 (–CH3); MS (ESI): 177.00 (M+).

2-Benzylidenehydrazinecarboxamide (3) In 50 mL of methanol, 5.0 g (66.6 mmol) ofsemicarbazide was dissolved and added with 6.8 mL (66.7 mmol) of benzaldehyde stirredfor 2 h. The obtained precipitate was washed with cold ethanol and diethyl ether and then driedunder high vacuum for 2 h. Yield 5.54 g (51 %); m.p. 170–172 °C; IR (KBr, cm−1): v 3,458.37(NH), 3,253 (NH2), 2,933.73, 2,991.59 (C–H), 1,689.64 (C = O), 1,647.21 (C = N); 1H NMR(D2O, 400 MHz): δ 6.588 (s, 1H, NH), 6.588 (s, 2H, NH2), 7.10–8.32 (m, 6H, Ar–CH), 10.35(s, 1H, HC = N); 13C NMR: δ 156.89 (C = O), 139.33 (N = C), 126.59–134.81(Ph); MS (ESI):163.00 (M+).

N′,N″-(Ethane-1,2-diylbis(diphenylphosphoranylyilidene))bis(4-(tert-butyl)benzohydrazide)(4) To 2.774 g (6.96 mmol) of dppe in 60 mL of CCl4, 0.35 mL (6.96 mmol) of bromine in20 mL of CCl4 was added dropwise at ice-cold temperature. The mixture was refluxed for 2 hand then cooled to room temperature. A pale yellow precipitate (Ph3PBr2) was obtained. To

598 Appl Biochem Biotechnol (2014) 173:596–608

this, 1.33 g (6.96 mmol) t-butyl phenyl hydrazide was added, followed by dropwise addition of1.94 mL (13.92 mmol) of triethylamine in 50 mL of CCl4. The mixture was stirred for 12 h atroom temperature. The precipitate (Et3N·HBr) was filtered off, and the filtrate was subjected tovacuum to obtain a colorless crystalline solid product. Yield 2.54 g (47 %); m.p. 133–134 °C;IR (KBr, cm−1): v 3,442.94 (NH), 2,939.52 (C–H), 1,672.28 (C = O), 1,610.64 (C = C),1,172.72 (P = N); 1H NMR: δ 1.30 (s, 9H, CH3), 2.13 (s, 4H, CH2), 7.42–7.82 (m, 28H, Ph),8.50 (s, 2H, NH); 13C NMR: δ 15.6 (P–CH2), 31.1 (CH3), 34.9 (CMe3), 125.6–137.0 (Ph),168.6 (NC = O); 31P-NMR: δ 31.7 (s).

2-Cyclohexylidenehydrazine carboxamide (5) To 1.002 g (6.13 mmol) of semicarbazide and1.5 g (18.2 mmol) of sodium acetate, 2 mL of cyclohexanone was added. A white precipitatewas obtained and washed with water. The residual solid was dried under high vacuum for 4 h.Yield 0.79 g (82 %); m.p. 160–161 °C; IR (KBr, cm−1): v 3,464.15 (NH), 3,253.91(NH2),2,929.87, 3,136.25 (C–H), 1,689.64 (C = O), 1,662.64 (C = N); 1H NMR: δ 9.062 (s, 1H, NH),6.151 (s, 2H, NH2), 1.51–1.58 (m, 6H, CH2), 2.15–2.18 (t, 2H, CH2), 2.27–2.29 (t, 2H, CH2);13C NMR: δ 156.89 (C = O), 139.33 (N = C), 10.2–40.2 (CH2); MS (ESI): 155.27 (M+).

The data obtained for the synthesized compounds 1–3 and 6 is comparable with theliterature reports [41–43]. Our attempts to isolate the compound 6a by the reaction of 5 andPh3PBr2 completely failed, and it was found that Ph3PO (6) was the major product due to thehydrolysis of 6a as shown in Scheme 2.1

Methods

UV-Vis Spectrophotometric Analysis

The absorbance of various ligands and their DNA interaction studies were carried out througha wave scan ranging from 200 to 800 nm. The UV-Vis spectra were recorded on a SYSTRONICS AU-2701 UV-Vis spectrophotometer. The absorbance spectrum of and the interac-tion of constant concentration of ligand with different concentrations of DNA (10, 20, 30, 40,50 μg) were recorded.

FT-IR Spectral Analysis

Infrared spectra were recorded on a Shimadzu IRAffinity-1 spectrophotometer (DTGS detec-tor, Ni–chrome source and KBr beam splitter). Spectra were collected and treated using theOMNIC software supplied by the manufacturing company of the spectrophotometer. Solutionspectra were recorded after 1 h of incubation, using AgBr windows. In the present

1 The general procedure was as follows: To 0.643 g (2.454 mmol) of triphenylphosphine in 30 mL of CCl4,0.126 mL (2.454 mmol) of bromine in 20 mL of CCl4 was added dropwise at ice-cold temperature. The mixturewas refluxed for 2 h and then cooled to room temperature. A pale yellow precipitate (Ph3PBr2) was obtained andused without isolation. To the reaction mixture, 0.2 g (1.227 mmol) semicarbazide was added, followed bydropwise addition of 0.69 mL (4.908 mmol) of triethylamine in 50 mL of CCl4. The mixture was refluxed for12 h and then cooled to room temperature. The precipitate has formed was filtered off and dissolved in CHCl3.Et3N·HBr salt was washed out with water in a separating funnel. The CHCl3 layer was dried with anhydrousNa2SO4 (3 g) and filtered. Then, the organic solvent was evaporated, and the residual solid was dried under highvacuum for 2 h. The colorless solid was found out to be Ph3PO (6). Yield 0.677 g (94 %); m.p. 154–158 °C; IR(KBr, cm−1): v 1,190.08 (P = O); 1H NMR: δ 7.12–8.18 (m, Ph); 13C-NMR: δ 128.59–133.12 (Ph); 31P NMR: δ29.43 (P = O); MS (ESI): 277.20 (M+).


investigation, the binding propensity of ligand (3 mg/ml) was examined with DNA (5 mg/ml)through the FT-IR spectrum. The shift in the spectral formation of synthetic ligand-DNAadduct was observed.

Molecular Docking Simulation Studies

The Protein Data Bank (PDB) is the worldwide library for structural data of biologicalmacromolecules, which is established in Brookhaven National Laboratories (BNL) in 1971.It contains structural information of the macromolecules determined by X-ray crystallographic,NMR methods, etc.2 Hence, the DNA target of our interest 1DSC (an octamer complexed withactinomycin D) (Table 1) was selected from this data bank. The original ligand was removedfrom target DNA, and the nucleotide base pairs (5′- D (*GP *AP* AP* GP* CP* TP* TP* C)-3′) were used for the particular analysis. The receptor DNA (1DSC) and the syntheticchemical compound were taken for in silico docking studies. Energy minimization for eachsynthetic chemical compound was performed by using UCSF Chimera. The UCSF Chimeraprogram (http://www.cgl.ucsf.edu/chimera) was used to prepare the structures for input toAutoDock 4.0 (http://mgltools.scripps.edu) by adding Gasteiger charges (computed usingAntechamber) and running 10,000 steps of energy minimization. The docking simulation ofthe chosen DNAwith the chemical compounds 2-(propan-2-ylidene) hydrazine carboxamide,N′-(propan-2-yilidene) nicotinohydrazide, 2-benzylidene hydrazinecarboxamide, N′,N″-(eth-ane-1,2-diylbis(diphenylphosphoranylyilidene))bis(4-(tert-butyl)benzohydrazide),2-cyclohexylidene hydrazine carboxamide, and triphenylphosphine oxide was explored byACD ChemSketch and Molecular Docking software (Autodock 4.0). This server integratesLamarckian genetic algorithms. Further, the above said six compounds were investigated fortheir hypothesized interaction with DNA via docking and their relative stabilities wereevaluated using molecular dynamics, free energy simulations, and their binding affinities.All the parameters used in docking server were selected by default.

Results and Discussion

The targeted hydrazides (2 and 4) and semicarbazide derivatives (1, 3, 5) were synthesized(Fig. 1) by reacting equimolar quantities of carbonyl compounds with corresponding hydra-zides (Scheme 1). The resulting precipitates were filtered off and washed with cold ethanol anddiethyl ether. The attempts to isolate the product 6a from phosphorylation of 5 failed, but theformation of 6 was observed during work-up of the reaction mixture (Scheme 2).3 All thesynthesized compounds were analyzed by spectroscopic methods using UV-Vis absorptionspectra, FT-IR, 1H 13C NMR, 13C NMR, 31P NMR, and GC-MS data.

The IR spectra of the hydrazide and semicarbazide derivatives were recorded in the range of4,000–200 cm−1. The infrared spectra of all the semicarbazide derivatives (1, 3, and 5)displayed the characteristic absorption bands in the region of 3,500–3,600 cm−1 (NH) assinglets and in the region of 3,200–3,300 cm−1 (NH2) as doublets. In

1H NMR, 1, 3, and 5showed the broad signals for –NH and –NH2 protons in the range of δ 9.0 to 10.0 and δ 6.0 to7.0, respectively. In addition to this, 13C NMR data exhibited the peaks corresponding toC = O and C = N in the range of δ 150–170 and δ 138–150, respectively.

2 See footnote 1.3 See footnote 1.


http://www.cgl.ucsf.edu/chimera

http://mgltools.scripps.edu/

In compound 2, the infrared bands at 3,441.01 and 1,649.14 cm−1 are assigned to the νNHand νC = O vibrations, respectively. 1H NMR spectra of hydrazide derivatives 2 and 4demonstrated the signals for –NH proton in the region of δ 8.0 to 10.0. Also, the twononequivalent methyl groups in isopropylidene moiety of 2 were appeared at δ 2.023 and1.906. Moreover, 13C NMR of 2 gave the peaks at δ 166.46 for C = O group and 162.41 forN = C. Apart from the infrared absorption bands at 3,442.94 (for NH) and 1,672.28 (for C = O)similar to 2, compound 4 showed a new band at 1,172.72 cm−1 assigned for P = N group. Forcompound 4, two methylene groups between two phosphorus atoms were shown at δ 2.13 as abroad signal in the 1H NMR spectrum. Also, a peak at δ 168.6 confirms the presence of“NC = O” group by 13C NMR. 31P NMR spectrum of 4 showed a singlet at δ 31.7, indicatingthat both the diphenylphosphino groups are equivalent.

DNA Interaction Studies

The hydrazide and semicarbazide derivatives 1–5 and the unexpected hydrolysis product 6(OPPh3) were evaluated for their DNA binding abilities with CT-DNA using UV-Vis andinfrared spectroscopic methods.

Table 1 The free energy bindingscore for the chemical compoundsdocked with DNA

Compound Binding energy (kcal/mol)

1 −5.42 −4.83 −4.64 −5.75 −6.26 −7.2

Scheme 1 Synthesis of hydrazide derivatives


Compound (1) DNA Adducts

Evidence for binding of 1with DNA duplex was noticed by a significant change in the patternsof UV-Vis absorption bands, i.e., a shift from 232 to 234 nm and formation of a new band at256 nm. The shift to a longer wavelength is a consequence of an ordered stacking of the1-(propan-2-ylidene)semicarbazide (1) (Fig. 2(1)). In addition, the intercalating surface isentrapped between the base pairs and stabilized electronically in the helix by p–p stackingand dipole–dipole interactions (Fig. 2) [44, 45].

Infrared bands for free DNA spectrum showed at 1,710 (guanine), 1,663 (thymine),1,608 (adenine), and 1,491 cm−1 (cytosine) as reported earlier [44–50]. It is importantto note that the addition of CT-DNA to 1-(propan-2-ylidene)semicarbazide (1) showedan increase in the vibrational bands of guanine and cytosine at 1,691.57 and1,497 cm−1, respectively. The interaction of 1 with guanine base was observed bychanges in the band positions from 1,710 to 1,691.57 cm−1, which confirms theexternal binding of 1 with DNA.

The bands observed at 1,234.44 and 1,018.41 cm−1 are characteristic features of 1-(propan-2-ylidene)semicarbazide (1)-phosphate binding because of an increase in the intensity ofphosphate stretching vibrations. The deoxyribose of DNA shows a band at 968 cm−1 andshifts to 966.34 cm−1 upon addition of 1. This indicates the interaction of deoxyribose with 1.Upon addition of DNA to 1, the N–O stretch and C–H bending interaction wereobserved at 1,413.82 and 1,479.40 cm−1, respectively. Further, the interaction of 1with CT-DNA was shown through C6 = O of guanine and C4 = O of thymine byformation of 1,581.63-cm−1 band (Fig. 3a).


The interaction of N′,N″-(ethane-1,2-diylbis(diphenylphosphoranylyilidene))bis(4-(tert-butyl)benzohydrazide) (4) with CT-DNAwas indicated by the shifts of infrared absorption bands ofthymine and cytosine from 1,663 to 1,654.92 cm−1 and 1,491 to 1,483.26 cm−1, respectively.The infrared absorptions were observed at 1,236, 1,087, and 1,070 cm−1 due to the increase inthe intensity of the phosphate stretching vibration as a result of 4-phosphate binding. Theappearance of bands at 1,532 instead of 1,633 cm−1 can be characteristic vibrations of C6 = Oof guanine and C4 = O of thymine. The bands at 1,439, 1,364 and 3.305 cm−1 are thecharacteristic feature of bending interaction of C–H, N–O stretch, and O–H bond shifting,respectively. Ligand 4 shows binding with deoxyribose sugar of DNA through a shift from 968to 964.41 cm−1, disappearance of –OH group, and subsequent incorporation of C = CHindicated by 3,055.24 cm−1 band (Fig. 3b). One of the usual bands of 4 at 234 nmgets shifted to 246 nm upon addition of different concentrations of CT-DNA similarto S8-DNA (Fig. 2(4)).

Scheme 2 (i) PPh3, Br2, CCl4, 3 h at 60 °C



The FT-IR analysis shows the binding of triphenylphosphine oxide (6) to thymine andcytosine, which is evident by band shifting from 1,663 to 1,655 cm−1 and 1,491 to1,483 cm−1, respectively. The characteristic positive bands at 1,236, 1,093, and1,072 cm−1 are due to the increase in the intensity of the phosphate stretchingvibrations as a result of its interaction with ligand 6. On addition of 6 to DNA, theappearance of a moderate intense band at 1,026.13 cm−1 due to alcoholic C–O stretchand a sharp band at 1,438.9 cm−1 for bending C–H vibrations was observed. The

(1) (4)

(6)

Fig. 2 The UV-Vis spectroscopic analysis on the interaction of CT-DNAwith the derivatives of semicarbazideand hydrazides and OPPh3 between the aromatic heterocyclic base pairs


disappearance of an –OH group as well as incorporation of an olefinic group(C = CH2 or C = CH) is indicated by the appearance of a band at 3,057 cm−1

.

The sharp DNA band at 968 cm−1 is a characteristic of C–C and C–O vibrationstretch of deoxyribose sugar and gets shifted to 966 cm−1 due to the interaction of 6with deoxyribose of CT-DNA (Fig. 3c). When ligand 6 is mixed with DNA, theUV-Vis absorption spectrum shows a hypsochromic shift (i.e., decrease in the wave-length of absorbance bands) from 220 to 212 nm. This is an indication of theintercalation of 6 through DNA duplex (Fig. 2(6)). Increasing the concentration ofligand causes helical destabilization and also prevents absorbance of light energy [48].

Conformational Energy of Six Synthetic Compounds

The investigation of DNA (receptor) interaction with six different synthetic molecules (ligands1–6) was performed to find the conformational energy of these molecules through Autodockserver. Each autodock run predicts the binding conformation, produce a value for free energyof binding (FEB) in kilocalories per mole and an estimated inhibitory concentration (Ki) inmicromolars. The lowest conformation energy shows the best interaction between ligand andreceptor. Hence, each compound is subjected for its validation of binding energy and ligandefficacy. The ranking of ligands was based on the scores generated by the docking server. Theligands (1–6) were accepted poses with the receptor 1DSC. The free energy binding score for

Fig. 3 FT-IR interaction study of compounds with DNA


the ligands docked with DNA was given in Table 1. The docking calculation producedreasonable binding modes (Fig. 4).

The receptor molecule is kept rigid, and the ligand being docked is usually flexiblethroughout the docking program. A grid-based approach is used to reduce the overall runtime of the docking simulation and to approximate the energy calculations used by the energyfunction. The grid formed for the DNA and the search space was a box with xyz dimensions of62 Å×62 Å×32 Å. The binding energy value of each compound differs due to the location ofits atoms present in ligand. The docking results illustrate the van der Waal force in associationwith the hydrogen bonding. When the van der Waal energies are positive, it is an indicationthat the ligand is not fitting well into the active site.

But the results of the study show that the van der Waal force energies are considerablynegative which in turn proves that all the six synthetic compounds are fitting well in to theDNA molecule. Each Autodock run shows ten conformations which are present in rank order.Hence, the first conformation is the best form having the lowest binding energy. Therefore,ligand 6 showed the lowest conformation energy among ligands.

Among semicarbazide derivatives (1, 3, 5), the alkyl substituted ligands (1 and 5) showedbetter binding energy than the aromatic ring containing 3. The increasing order of bindingenergies of semicarbazide derivatives is 5>1>3 as shown in Table 1. Strikingly, the hydrazide

Fig. 4 Docking structures of compounds with DNA and their binding energy score


with phospholidene moiety 4 showed a significant binding energy than its analogue 1.Among the tested molecules, surprisingly the Ph3PO molecule showed superior bind-ing with DNA. This can be attributed to the strong basicity of the phosphoryl oxygen(P = O) in solution.

Conclusion

On the basis of IR, UV-Vis absorbance spectra, NMR, and mass spectral data, it is possible toassign the structures of synthesized hydrazide and semicarbazide compounds. The bindingstudies clearly reveal that these compounds have significant interactions with DNA. It isinteresting to note that semicarbazide derivatives with aliphatic substituents showed betterDNA binding than the aromatic substituents. We are optimistic that our future investigationson biological properties of various hydrazide and semicarbazide based silicon(IV) andphosphorus(V) compounds may lead to the development of promising classes of specificand effective pharmaceutical agents.

Acknowledgments Support for this work from DST-SERB, New Delhi, India (ref. no. SR/S1/IC-30/2011) isgratefully acknowledged. Mr. Janardan Sannapaneni thanks DST for the project fellowship. Mr. Suman Pothini isgrateful to VIT University for the research fellowship. Dr. ASRK and his group members thank DST-VIT-FISTfor NMR and SIF-VIT for other instrumentation facilities.

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Evaluation of DNA Binding with Some Sele cted Hydrazide and Semicarbaz ide De rivati ves

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