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Synton 3-(anthracen-9-yl)-2-cyanoacryloyl chloride 4 chu siamin nitrogen nucleophile hrang hrang nena a inremna hmangin heterocyclic compound active tak tak chi hrang hrang siam nan hman a ni. Heterocyclic compound siam chhuah tinte structure chu spectroscopic leh elemental analysis hmangin uluk takin an characterize a. Novel heterocyclic compound 13 zinga 10 chuan multidrug-resistant bacteria (MRSA) laka a thawh thatna tichaktu an lantir a ni. Chung zingah chuan compound 6, 7, 10, 13b, leh 14 te hian antibacterial activity an nei sang ber a, inhibition zone cm 4 vel hnaih an nei a ni. Mahse, molecular docking study-ah chuan compound te hian MRSA resistance atana target pawimawh tak penicillin-binding protein 2a (PBP2a) nen binding affinities hrang hrang an nei tih hmuhchhuah a ni. Compound thenkhat 7, 10 leh 14 te hian co-crystallized quinazolinone ligand nena khaikhin chuan PBP2a active site-ah binding affinity leh interaction stability sang zawk an nei a. Chumi danglamna chu compound 6 leh 13b te hian docking score hniam zawk nei mahse antibacterial activity nasa tak an la lantir tho a, compound 6 hian MIC (9.7 μg/100 μL) leh MBC (78.125 μg/100 μL) value a nei hniam ber a ni. Docking analysis-ah hian hydrogen bonding leh π-stacking telin inzawmna pawimawh tak tak a awm tih hmuhchhuah a ni a, a bik takin residue Lys 273, Lys 316 leh Arg 298 te nen an inzawm tih hmuhchhuah a ni a, chungte chu PBP2a crystal structure-a co-crystallized ligand nena inzawm nia hriat a ni. Heng residue te hi PBP2a enzymatic activity atan a pawimawh hle. Heng results te hian synthesized compounds te hi anti-MRSA damdawi beisei awm tak angin an thawk thei tih a tilang a, hei hian molecular docking leh bioassays te inzawmkhawm a, therapeutic candidate tha tak tak hriatchhuah a pawimawhzia a tilang chiang hle.
Kumin kum zabi hmasa berah khan zirchianna hmalakna chu awlsam taka hmuh theih bul tanna hmanga antimicrobial activity nei heterocyclic system thar engemaw zat siam chhuahna atana kalphung leh hmanraw thar, awlsam tak siam chhuah a ni ber a ni.
Acrylonitrile moieties hi heterocyclic system mak tak tak tam tak siamna atana bul tanna pawimawh takah ngaih a ni a, a chhan chu reactive compound sang tak an nih vang a ni. Chubakah, tun hnaiah 2-cyanoacryloyl chloride derivatives hi damdawi lama hmanraw pawimawh tak tak, damdawi intermediates1,2,3, anti-HIV, antiviral, anticancer, antibacterial, antidepressant leh antioxidant agents hmahruaitu4,5,6,7,8,9, Tun hnaiah anthracene leh a derivatives te biological efficacy, an antibiotic, anticancer11,12, antibacterial13,14,15 leh insecticidal property16,17 te hian ngaihven a hlawh hle a ni18,19,20, Acrylonitrile leh anthracene moieties awmna antimicrobial compound te chu Figure 1 leh 2 ah hian tarlan a ni.
World Health Organization (WHO) (2021) chhinchhiah dan chuan antimicrobial resistance (AMR) hi khawvel pum huapa hriselna leh hmasawnna atana hlauhawm tak a ni22,23,24,25. Damlote tihdam theih a ni lo va, damdawi ina awm rei zawk leh damdawi man to zawk mamawhna bakah thihna leh rualbanlote a tipung bawk. Antimicrobial tha tak tak a awm loh avangin natna chi hrang hrang enkawlna a hlawhchham fo thin a, a bik takin chemotherapy leh surgery lian tham tak tak neih laiin.
World Health Organization 2024 report-in a tarlan danin, methicillin-resistant Staphylococcus aureus (MRSA) leh E. coli te hi natna hrik pawimawh ber list-ah hian a tel a ni. Bacteria pahnihte hian antibiotics tam tak an do thei a, chuvangin enkawl leh thunun harsa tak takte an entir a, he harsatna sutkian nan hian antimicrobial compound thar leh tangkai tak tak siam chhuah a ngai nghal a ni. Anthracene leh a derivatives te hi antimicrobial hriat hlawh tak an ni a, Gram-positive leh Gram-negative bacteria te pawh a thawk thei a ni. He zirchianna hian a tum ber chu heng natna hrik, hriselna atana hlauhawm tak takte do thei tur derivative thar siam chhuah a ni.
World Health Organization (WHO) chuan bacterial pathogens tam tak chu antibiotics tam tak lakah an do thei tih a tarlang a, chung zingah chuan khawtlang leh hriselna enkawlna hmuna hri kai chhan tlangpui methicillin-resistant Staphylococcus aureus (MRSA) pawh a tel. MRSA vei damlote chu damdawi hmanga kai damlote aiin 64% zetin an thihpui zawk nia sawi a ni. Chu bakah, E. coli hian khawvel pumah hlauhawmna a thlen a, a chhan chu carbapenem-resistant Enterobacteriaceae (ie, E. coli) laka invenna line hnuhnung ber chu colistin a ni a, mahse tun hnaiah ram engemaw zatah colistin-resistant bacteria hmuhchhuah a ni. 22,23,24,25 a ni
Chuvangin, World Health Organization Global Action Plan on Antimicrobial Resistance26-in a tarlan dan chuan antimicrobial thar hmuhchhuah leh siam chhuah hi hmanhmawhthlak tak a ni. Anthracene leh acrylonitrile te hian antibacterial27, antifungal28, anticancer29 leh antioxidant30 agents an nih theihna ropui tak chu paper chhuah tam takah tarlan a ni. Hemi chungchangah hian heng derivatives te hi methicillin-resistant Staphylococcus aureus (MRSA) laka hman tur candidate tha tak an ni tih sawi theih a ni.
Tun hmaa literature review-te khan heng class-a derivative thar siam chhuah tumin min fuih a. Chuvangin, tun zirchianna hian anthracene leh acrylonitrile moieties awmna heterocyclic system thar siam a tum a, an antimicrobial leh antibacterial efficacy te endik a, molecular docking hmanga penicillin-binding protein 2a (PBP2a) nena an binding interaction awm thei te zirchian a tum a ni. Tun hmaa zirchiannate atanga innghatin, tun zirchianna hian heterocyclic systems synthesis, biological evaluation, leh computational analysis te chu a chhunzawm zel a, antimethicillin-resistant Staphylococcus aureus (MRSA) agents beisei awm tak tak, PBP2a inhibitory chak tak nei te chu a hmuchhuak ta a ni hnathawh31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49.
Tuna kan zirchianna hian anthracene leh acrylonitrile moieties awmna novel heterocyclic compound siam leh antimicrobial evaluation chungchang a ngaihtuah ber a ni. 3-(anthracen-9-yl)-2-cyanoacryloyl chloride 4 siamin heterocyclic system thar siamna atana building block atan hman a ni.
Compound 4 structure chu spectral data hmangin an chhut a. 1H-NMR spectrum-ah chuan CH= 9.26 ppm-ah a awm tih a lang a, IR spectrum-ah chuan carbonyl group 1737 cm−1-ah leh cyano group 2224 cm−1-ah a awm tih a lang a, 13CNMR spectrum-ah pawh structure ruahman chu a nemnghet bawk (Experimental section en rawh).
3-(anthracen-9-yl)-2-cyanoacryloyl chloride 4 siamna chu aromatic group 250, 41, 42, 53 te chu ethanolic sodium hydroxide solution (10%) hmanga hydrolysis hmanga acid 354, 45, 56 siam a ni a, chu chu tui bath-ah thionyl chloride hmanga tihfai a ni a, pek a ni acryloyl chloride derivative 4 chu yield sang tak (88.5%) a ni a, Figure 3-a kan hmuh ang hian.
Antibacterial efficacy beisei angin heterocyclic compound thar siam nan acyl chloride 4 chu dinucleophiles hrang hrang nen an inrem a.
Acid chloride 4 chu hydrazine hydrate hmangin 0°-ah darkar khat chhung an enkawl a. Vanduaithlak takin pyrazolone 5 hmuh tur a awm lo. He product hi acrylamide derivative a ni a, a structure chu spectral data hmangin a nemnghet a ni. A IR spectrum-ah chuan C=O chu 1720 cm−1-ah, C≡N chu 2228 cm−1-ah leh NH chu 3424 cm−1-ah absorption band a ni. 1H-NMR spectrum ah hian olefin proton leh NH proton te exchange singlet signal 9.3 ppm ah a lang a (Experimental Section en la).
Acid chloride 4 mole hnih chu phenylhydrazine mole khat nen an inrem a, N-phenylacryloylhydrazine derivative 7 chu yield tha tak (77%)-in an hmu a (Figure 5). 7 structure hi infrared spectroscopy data hmangin a nemnghet a, 1691 leh 1671 cm−1-ah C=O group pahnih absorption, 2222 cm−1-ah CN group absorption leh 3245 cm−1-ah NH group absorption, a 1H-NMR spectrum-ah CH group 9.15 leh 8.81 ppm leh NH-ah a lang bawk proton chu 10.88 ppm a ni (Experimental section en rawh).
He zirchiannaah hian acyl chloride 4 leh 1,3-dinucleophiles te inrem dan an zirchiang a. Acyl chloride 4 chu 1,4-dioxane-a 2-aminopyridine hmanga TEA base anga room temperature-a enkawl chuan acrylamide derivative 8 (Figure 5) a hmu a, a structure chu spectral data hmangin hriatchhuah a ni. IR spectra-ah chuan cyano absorption band chu 2222 cm−1-ah, NH chu 3148 cm−1-ah, leh carbonyl-te chu 1665 cm−1-ah a inzawm a; 1H NMR spectra hmangin olefin protons 9.14 ppm-ah a awm tih a chiang a (Experimental Section en rawh).
Compound 4 chu thiourea nen an inrem a, pyrimidinethione 9 a lo chhuak a; compound 4 chu thiosemicarbazide nen an inrem a, thiopyrazole derivative 10 a lo chhuak ta a ni (Figure 5). Compound 9 leh 10 te structure chu spectral leh elemental analysis hmangin an nemnghet a (Experimental section en rawh).
Compound 4 leh thiocarbazide chu 1,4-dinucleophile anga siamin tetrazine-3-thiol 11 siam a ni a (Figure 5), a structure chu spectroscopy leh elemental analysis hmangin a nemnghet a ni. Infrared spectrum-ah chuan C=N bond chu 1619 cm−1-ah a lang a. Chutih rual chuan a 1H-NMR spectrum chuan aromatic protons multiplate signals 7.78–8.66 ppm leh SH protons 3.31 ppm ah a vawng reng bawk (Experimental Section en la).
Acryloyl chloride 4 hian 1,2-diaminobenzene, 2-aminothiophenol, anthranilic acid, 1,2-diaminoethane, leh ethanolamine te nen 1,4-dinucleophiles angin an inrem a, heterocyclic system thar a siam a (13–16).
Heng compound siam tharte structure hi spectral leh elemental analysis hmangin an nemnghet a (Experimental section en la). 2-Hydroxyphenylacrylamide derivative 17 chu 2-aminophenol nen dinucleophile anga reaction hmangin an hmu a (Figure 6), a structure chu spectral leh elemental analysis hmangin an nemnghet bawk. Compound 17 infrared spectrum atanga a lan dan chuan C=O leh C≡N signal te chu 1681 leh 2226 cm−1 ah a lang a ni. Hetihlai hian a 1H-NMR spectrum chuan olefin proton singlet signal chu 9.19 ppm-ah a vawng reng a, OH proton chu 9.82 ppm-ah a lang bawk (Experimental section en rawh).
Acid chloride 4 chu nucleophile pakhat (eg, ethylamine, 4-toluidine, leh 4-methoxyaniline) nen dioxane-ah solvent atan leh TEA chu catalyst atan room temperature-ah an inrem a, green crystalline acrylamide derivatives 18, 19a, leh 19b a awm a ni. Compound 18, 19a, leh 19b te elemental leh spectral data chuan heng derivatives te structure hi a nemnghet a (Experimental Section en la) (Figure 7).
Synthetic compound hrang hrangte antimicrobial activity screening hnuah Table 1 leh Figure 8-a kan hmuh angin result hrang hrang a awm a (figure file en rawh). Compound test zawng zawng hian Gram-positive bacterium MRSA laka inhibition degree hrang hrang an nei a, Gram-negative bacterium Escherichia coli erawh chuan compound zawng zawng lakah hian a dodal vek thung. Compound test te hi MRSA laka inhibition zone diameter a zirin category pathum ah then theih a ni. Category hmasa ber chu active ber a ni a, compound panga (6, 7, 10, 13b leh 14) a awm a ni. Heng compound-te inhibition zone diameter hi cm 4 vel a ni a; he category-a compound active ber chu compound 6 leh 13b te an ni. Category pahnihna chu moderately active a ni a, compound panga dang (11, 13a, 15, 18 leh 19a) a awm bawk. Heng compound te inhibition zone hi 3.3 atanga 3.65 cm inkar a ni a, compound 11 hian inhibition zone lian ber 3.65 ± 0.1 cm a nei a ni. A lehlamah chuan group hnuhnung berah hian antimicrobial activity hniam ber (3 cm aia tlem) compound pathum (8, 17 leh 19b) an awm a. Figure 9-ah hian inhibition zone hrang hrangte insem dan tarlan a ni.
Compound test tawhte antimicrobial activity chhui chian belh a nih chuan compound tinte MIC leh MBC te chu an teh a ni. Results chu a inang lo deuh (Table 2, 3 leh Figure 10-a kan hmuh angin (figure file en rawh)), compound 7, 11, 13a leh 15 te chu compound tha ber anga classified leh niin a lang. MIC leh MBC value hniam ber (39.06 μg/100 μL) an nei ve tho. Compound 7 leh 8 te hian MIC value hniam zawk (9.7 μg/100 μL) nei mahse an MBC value erawh a sang zawk (78.125 μg/100 μL). Chuvangin, a hmaa kan sawi tawh compound aiin chak lo zawkah an ngai ta a ni. Mahse, heng compound paruk te hi test zingah chuan a hlawk ber a, an MBC value chu 100 μg/100 μL hnuai lam a nih avangin.
Compound (10, 14, 18 leh 19b) te hi test tawh compound dangte nena khaikhin chuan an active lo zawk a, an MBC value chu 156 atanga 312 μg/100 μL inkar a nih avangin. A lehlamah chuan compound (8, 17 leh 19a) te chu MBC value sang ber (625, 625 leh 1250 μg/100 μL, a hnuaia mi) an neih avangin beisei awm lo ber an ni.
A tawp berah chuan Table 3-a tolerance level tarlan ang hian test-na compound te hi an hnathawh dan azirin category hnih ah then theih a ni a, chungte chu bactericidal effect nei compound (7, 8, 10, 11, 13a, 15, 18, 19b) leh antibacterial effect nei compound (6, 13b, 14, 17, 19a) te an ni. Chung zingah chuan compound 7, 11, 13a leh 15 te hi duhthusam a ni a, chungte chuan concentration hniam tak (39.06 μg/100 μL)-ah killing activity an lantir a ni.
Compound 13 test zinga 10 chuan antibiotic-resistant methicillin-resistant Staphylococcus aureus (MRSA) laka an do theihna an nei tih an hmuchhuak. Chuvangin, antibiotic-resistant pathogens tam zawk (a bik takin local isolates covering pathogenic Gram-positive leh Gram-negative bacteria) leh pathogenic yeasts hmanga screening neih belh a tha a, chubakah compound tinte cytotoxic testing neih a tha a, a him leh him loh enfiah a tha bawk.
Molecular docking study neih a ni a, heng compound siamte hian methicillin-resistant Staphylococcus aureus (MRSA)-a penicillin-binding protein 2a (PBP2a) inhibitor an nih theih dan an zirchiang a ni. PBP2a hi bacterial cell wall biosynthesis-a inrawlh enzyme pawimawh tak a ni a, he enzyme hi tihkhawtlai hian cell wall siamna a tibuai a, a tawpah chuan bacteria lysis leh cell thihna a thlen thin Docking result chu Table 4-ah tarlan a ni a, supplementary data file-ah chipchiar zawkin tarlan a ni a, result-ah hian compound engemaw zatin PBP2a tan binding affinity chak tak an lantir tih a tarlang a, a bik takin key active site residue Lys 273, Lys 316, leh Arg 298 te a ni a, hydrogen bonding leh π-stacking te pawh telna inzawmna chu a inang hle a ni co-crystallized quinazolinone ligand (CCL), hei hian heng compound te hi inhibitor chak tak an nih theih thu a tarlang.
Molecular docking data bakah hian computational parameter dangte chuan PBP2a inhibition hi heng compound-te antibacterial activity hmuhchhuahna atana mawhphurtu pawimawh ber a nih thu nasa takin a tarlang a ni. Docking score leh root mean square deviation (RMSD) value te hian binding affinity leh stability chu a pholang lehzual a, hei hian he hypothesis hi a thlawp a ni. Table 4-a kan hmuh angin compound engemaw zatin binding affinity tha tak an lantir laiin, compound thenkhat (eg, 7, 9, 10, leh 14) te chuan co-crystallized ligand aiin docking score sang zawk an nei a, hei hian PBP2a active site residue te nen hian inzawmna chak zawk an nei thei tih a tilang a ni. Mahse, bioactive ber compound 6 leh 13b te hian ligand dangte nena khaikhin chuan docking score (-5.98 leh -5.63, a hnuaia mi ang hian) an nei tlem zawk a ni. Hei hian docking score hmangin binding affinity sawi lawk theih ni mah se, thil dang (eg, biological environment-a ligand stability leh molecular interactions) te pawhin antibacterial activity tehnaah hmun pawimawh tak an chang tih a tilang. Hriat tur pawimawh tak chu, synthesized compound zawng zawng RMSD value chu 2 Å hnuai lam a ni a, hei hian an docking pose te chu co-crystallized ligand binding conformation nen structurally a inmil tih a nemnghet a, hei hian PBP2a inhibitor chak tak an nih theihna chu a thlawp lehzual a ni.
Docking score leh RMS value te hian prediction hlu tak tak pe mahse, heng docking result leh antimicrobial activity inzawmna hi a hmasa berah chuan a chiang lo fo thin. PBP2a inhibition hi antimicrobial activity nghawngtu pawimawh tak a nih thu nasa takin thlawp mah se, danglamna engemaw zat chuan biological property dangte pawhin hmun pawimawh tak an chang tih a tilang. Compound 6 leh 13b te hian antimicrobial activity an nei sang ber a, inhibition zone diameter 4 cm leh MIC (9.7 μg/100 μL) leh MBC (78.125 μg/100 μL) value hniam ber an nei ve ve a, compound 7, 9, 10 leh 14 te nena khaikhin chuan docking score hniam zawk mahse hei hian a tilang a ni inhibition hian antimicrobial activity a tipung a, bacteria environment-a solubility, bioavailability leh interaction dynamics te pawh hian overall activity a nghawng bawk. Figure 11-ah hian an docking pose tarlan a ni a, hei hian compound pahnih hi binding score hniam tak nei mahse PBP2a key residue te nen an la inzawm thei tih a tilang a, hei hian inhibition complex chu a ti nghet thei a ni. Hei hian molecular docking hian PBP2a inhibition chungchangah hriatna pawimawh tak a pe a, mahse heng compound-te hian khawvel tak takah antimicrobial effect a neih dan hi a taka hriatthiam theih nan biological factor dangte ngaihtuah a ngai tih a tilang chiang hle.
PBP2a crystal structure (PDB ID: 4CJN) hmangin methicillin-resistant Staphylococcus aureus (MRSA) penicillin-binding protein 2a (PBP2a) nena docked compound 6 leh 13b active ber berte 2D leh 3D interaction map siam a ni. Heng map-te hian heng compound-te inzawmna (interaction pattern) hi re-docked co-crystallized quinazolinone ligand (CCL) nen an khaikhin a, hydrogen bonding, π-stacking, leh ionic interaction te ang chi inzawmna pawimawh tak takte a tarlang a ni.
Compound 7-ah pawh hetiang pattern hi hmuh a ni a, docking score sang tak (-6.32) a nei a, compound 10 nen pawh inhibition zone diameter (3.9 cm) a inang a, mahse a MIC (39.08 μg/100 μL) leh MBC (39.06 μg/100 μL) te chu a sang zawk hle a, hei hian antibacterial effect lantir nan concentration sang zawk a mamawh tih a tilang a ni. Hei hian compound 7 hian docking study-ah binding affinity chak tak nei mahse, bioavailability, cellular uptake, emaw physicochemical property dang emaw ang chi thilte hian a biological efficacy a tihtlem thei tih a tilang. Compound 7 hian bactericidal property nei mahse, compound 6 leh 13b nena khaikhin chuan bacteria thanna tur a titawp lo hle.
Compound 10 hian docking score sang ber (-6.40) nen danglamna nasa zawk a lantir a, hei hian PBP2a nena binding affinity chak tak a lantir a ni. Mahse, a zone of inhibition diameter (3.9 cm) chu compound 7 nen tehkhin theih a ni a, a MBC (312 μg/100 μL) chu compound 6, 7, leh 13b aiin a sang zawk tih a chiang a, hei hian bactericidal activity a chak lo zawk tih a tilang a ni. Hei hian docking prediction tha tak awm mahse, compound 10 hian MRSA tihlumna kawngah a hlawk lo zawk tih a tilang a, hei hi thil dang limiting factors solubility, stability, emaw bacterial membrane permeability tha lo vang te a ni. Heng results te hian PBP2a inhibition hian antibacterial activity-ah hmun pawimawh tak a chang a, mahse test tawh compound zinga biological activity danglamna hmuhchhuah chu a sawifiah kim lo tih hriatthiamna a thlawp a ni. Heng danglamnate hian antibacterial mechanisms inrawlh zawng zawng chiang taka hriat chian nan experimental analysis dang leh in-depth biological evaluation neih a ngai tih a tilang a ni.
Table 4 leh Supplementary Data File-a molecular docking result-te hian docking score leh antimicrobial activity inzawmna buaithlak tak a tarlang a ni. Compound 6 leh 13b te hian compound 7, 9, 10, leh 14 te aiin docking score hniam zawk nei mahse, antimicrobial activity sang ber an nei a ni. An interaction map (Figure 11-a kan hmuh) atanga a lan dan chuan an binding score hniam zawk mahse, PBP2a key residue te nen hydrogen bonds leh π-stacking interaction pawimawh tak tak an la siam a, chu chuan enzyme-inhibitor complex chu biologically beneficial takin a stabilize thei a ni. Docking score 6 leh 13b te hi a hniam hle chung pawhin, an antimicrobial activity tihpun hian inhibitor potential tehnaah docking data nen hian property dang, solubility, stability, leh cellular uptake te ngaihtuah tel a ngai tih a tilang. Hei hian compound tharte therapeutic potential dik taka tehna atana docking study leh experimental antimicrobial analysis te inzawmkhawm a pawimawhzia a tilang chiang hle.
Heng results te hian molecular docking hi binding affinity hrilhfiahna leh inhibition mechanism awm thei te hriatchhuahna atana hmanraw chak tak a nih laiin, antimicrobial efficacy hriat theihna atan chauh rinchhan tur a ni lo tih a tilang chiang hle. Molecular data atanga a lan dan chuan PBP2a inhibition hi antimicrobial activity tidanglamtu pawimawh tak a ni a, mahse biological activity inthlak danglamna chuan therapeutic efficacy tihsan nan physicochemical leh pharmacokinetic property dangte pawh optimize a ngai tih a tilang. Nakin lawka zirchiannaah chuan compound 7 leh 10 te chemical structure tihchangtlun a, bioavailability leh cellular uptake tihchangtlun dan tur ngaihtuah a ngai a, docking interaction chak tak chu antimicrobial activity tak takah a chantir theih nan. Zirna dang, bioassays leh structure-activity relationship (SAR) analysis te pawh tel hian heng compound te hi PBP2a inhibitor anga an hnathawh dan kan hriatthiamna tizau zawk tur leh antimicrobial agents tha zawk siam chhuah nan a pawimawh hle ang.
3-(anthracen-9-yl)-2-cyanoacryloyl chloride 4 atanga compound siamte hian antimicrobial activity degree hrang hrang an nei a, compound engemaw zatin methicillin-resistant Staphylococcus aureus (MRSA) a titawp nasa hle tih an lantir bawk. Structure-activity relationship (SAR) analysis-ah hian heng compound-te antimicrobial efficacy hnuaia structural feature pawimawh tak tak a awm tih hmuhchhuah a ni.
Acrylonitrile leh anthracene group pahnih awmna hi antimicrobial activity tihpunna atan a pawimawh hle tih a chiang. Acrylonitrile-a highly reactive nitrile group hi bacterial protein nena inzawmna siam awlsam nan a ngai a, chu chuan compound antimicrobial property a tipung a ni. Acrylonitrile leh anthracene pahnih awmna compound te hian antimicrobial effect chak zawk an lantir fo thin. Anthracene group aromaticity hian heng compound te hi a ti nghet lehzual a, an biological activity a tichak thei a ni.
Heterocyclic rings hman tan hian derivative engemawzat antibacterial efficacy nasa takin a tichangtlung a ni. A bik takin benzothiazole derivative 13b leh acrylhydrazide derivative 6 te hian antibacterial activity sang ber an nei a, inhibition zone chu cm 4 vel a ni. Heng heterocyclic derivatives te hian biological effects langsar zawk an lantir a, hei hian heterocyclic structure hian antibacterial effects ah hian hmun pawimawh tak a chang tih a tilang a ni. Chutiang bawkin compound 9-a pyrimidinethione, compound 10-a thiopyrazole, leh compound 11-a tetrazine ring te hian compound-te antibacterial property a tipung a, hei hian heterocyclic modification pawimawhzia a tilang lehzual a ni.
Compound siam chhuah zingah hian 6 leh 13b te hi antibacterial activity tha tak an neih avangin an langsar hle. Compound 6-a inhibitory concentration (MIC) tlem ber chu 9.7 μg/100 μL a ni a, bactericidal concentration (MBC) tlem ber chu 78.125 μg/100 μL a ni a, hei hian methicillin-resistant Staphylococcus aureus (MRSA) tihfai theihna tha tak a neihzia a tilang chiang hle. Chutiang bawkin compound 13b hian inhibition zone cm 4 a nei a, MIC leh MBC value a hniam a, hei hian antibacterial activity chak tak a neih thu a nemnghet a ni. Heng results te hian heng compound te bioefficacy tehna kawnga acrylohydrazide leh benzothiazole functional group te chanvo pawimawh tak a tarlang a ni.
Chumi danglamna chu compound 7, 10, leh 14 te hian antibacterial activity hniam tak an nei a, inhibition zone chu 3.65 atanga 3.9 cm inkar a ni. Heng compound te hian bacteria te hi tihhlum vek turin concentration sang zawk an mamawh a, hei hi an MIC leh MBC value sang lutuk hian a tilang chiang hle. Heng compound te hi compound 6 leh 13b aiin active lo zawk mahse, antibacterial potential nasa tak an la lantir tho a, hei hian heterocyclic ring-a acrylonitrile leh anthracene moieties te dah tel hian an antibacterial effect a tipung tih a tilang.
Compound te hian hnathawh dan hrang hrang an nei a, thenkhat chuan bactericidal property an nei a, thenkhat chuan bacteriostatic effect an nei bawk. Compound 7, 11, 13a, leh 15 te hi bactericidal an ni a, bacteria tihhlum vek tur chuan concentration hniam zawk an mamawh a ni. Chumi danglamna chu compound 6, 13b leh 14 te hi bacteriostatic an ni a, concentration hniam zawkah chuan bacteria thanna a titawp thei a, mahse bacteria tihhlum vek tur chuan concentration sang zawk a mamawh thung.
A pum puiin, structure-activity relationship analysis hian antibacterial activity nasa tak neih theih nan acrylonitrile leh anthracene moieties leh heterocyclic structures te luhtir a pawimawhzia a tarlang a ni. Heng results te hian heng structural components te optimization leh solubility leh membrane permeability tihchangtlunna tura siamthatna dang zawn chhuah hian anti-MRSA damdawi tha zawk siam chhuah a thlen thei tih a tilang.
Reagent leh solvent zawng zawng chu standard procedure (El Gomhouria, Egypt) hmangin tihthianghlim leh vawt vek a ni. Melting point hi GallenKamp electronic melting point apparatus hmanga chhut a ni a, siamthat ngai lovin report a ni. Infrared (IR) spectra (cm−1) chu Department of Chemistry, Faculty of Science, Ain Shams University-ah Thermo Electron Nicolet iS10 FTIR spectrometer (Thermo Fisher Scientific, Waltham, MA, USA)-ah potassium bromide (KBr) pellets hmangin record a ni.
1H NMR spectra chu GEMINI NMR spectrometer (GEMINI Manufacturing & Engineering, Anaheim, CA, USA) leh BRUKER 300 MHz NMR spectrometer (BRUKER Manufacturing & Engineering, Inc.) hmangin 300 MHz-ah lak a ni. Tetramethylsilane (TMS) chu deuterated dimethyl sulfoxide (DMSO-d7) nen internal standard atan hman a ni. NMR tehna hi Faculty of Science, Cairo University, Giza, Egypt-ah an ti a ni. Elemental analysis (CHN) hi Perkin-Elmer 2400 Elemental Analyzer hmanga tih a ni a, result hmuh chu chhut chhuah value nen a inmil tha hle.
Acid 3 (5 mmol) leh thionyl chloride (5 ml) inzawmkhawm chu tui bath-ah 65 °C-ah 4 h chhung an dah a. Thionyl chloride tam lutuk chu pressure tihhniam hnuaiah distillation hmangin an paih chhuak a. Chuta chhuak red solid chu an la khawm a, tihthianghlim belh ngai lovin an hmang ta a ni. Melting point: 200-202 °C, a rah chhuah: 88.5%. IR (KBr, ν, cm−1): 2224 (C≡N), 1737 (C=O) a ni. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 9.26 (s, 1H, CH=), 7.27-8.57 (m, 9H, heteroaromatization) a ni. A rilru a hah lutuk chuan a rilru a buai em em a, a rilru a hah lutuk chuan a rilru a buai em em bawk a. 13C NMR (75 MHz, DMSO-d6) δ (ppm): 115.11 (C≡N), 124.82–130.53 (CH anthracene), 155.34, 114.93 (CH=C–C=O), 162.22 (C=O); HRMS (ESI) m/z [M + H]+: 291.73111 a ni. Analyst a ni. C18H10ClNO (291.73) atana chhut chuan: C, 74.11; H, 3.46 a ni a; N, 4.80 a ni. Hmuhchhuah: C, 74.41; H, 3.34 a ni a; N, 4.66% a ni.
0°C-ah 4 (2 mmol, 0.7 g) chu anhydrous dioxane (20 ml)-ah a hmin a, hydrazine hydrate (2 mmol, 0.16 ml, 80%) chu dropwise-in dahin 1 h chhung stir a ni. Solid lo chhuak chu filtration hmangin an la khawm a, ethanol atanga recrystallized niin compound 6 a lo chhuak ta a ni.
Green crystals, melting point 190-192°C, 69.36% a chhuak a; IR (KBr) ν=3424 (NH), 2228 (C≡N), 1720 (C=O), 1621 (C=N) cm−1. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 9.3 (br s, H, NH, inthlak danglam theih), 7.69-8.51 (m, 18H, heteroaromatic), 9.16 (s, 1H, CH=), 8.54 (s, 1H, CH=); C33H21N3O (475.53) atana chhut chhuah zat: C, 83.35; H, 4.45 a ni a; N, 8.84 a ni. Hmuhchhuah: C, 84.01; H, 4.38 a ni a; N, 8.05% a ni.
Anhydrous dioxane solution (triethylamine drop tlemte awmna) 20 ml-ah 4 (2 mmol, 0.7 g) chu hmin la, phenylhydrazine/2-aminopyridine (2 mmol) dah la, room temperature-ah 1 leh 2 h chhung hrual rawh. Reaction mixture chu ice emaw tui emaw ah theh la, dilute hydrochloric acid hmangin acidify rawh. Solid inthen tawh chu filter off la, ethanol atanga recrystallize la, 7 hmu la, benzene atanga recrystallize la, 8 hmu rawh.
Green crystals, melting point 160-162°C, 77% a chhuak a; IR (KBr, ν, cm−1): 3245 (NH), 2222 (C≡N), 1691 (C=O), 1671 (C=O) cm−1. 1H-NMR (400 MHz, DMSO-d6): δ (ppm): 10.88 (s, 1H, NH, inthlak danglam theih), 9.15 (s, 1H, CH=), 8.81 (s, 1H, CH=), 6.78-8.58 (m, 23H, heteroaromatic) C42H26N4O2 (618.68) atana chhut chhuah zat: C, 81.54; H, 4.24 a ni a; N, 9.06 a ni. Hmuhchhuah: C, 81.96; H, 3.91 a ni a; N, 8.91% a ni.
4 (2 mmol, 0.7 g) chu anhydrous dioxane solution (triethylamine drop tlemte awmna) 20 ml-ah a hmin a, 2-aminopyridine (2 mmol, 0.25 g) chu dahin room temperature-ah 2 h chhung hrual a ni. Reaction mixture chu ice water-ah theh a, dilute hydrochloric acid hmangin acidified a ni. Precipitate lo awm chu filter off a ni a, benzene atangin recrystallized a ni a, green crystal 8 a awm a, a melting point chu 146-148 °C a ni a, yield chu 82.5% a ni A rilru a hah lutuk chuan a rilru a buai em em a, a rilru a hah lutuk chuan a rilru a buai em em bawk a. 3148 (NH), 2222 (C≡N), 1665 (C=O) cm−1. 1H NMR (400 MHz, DMSO-d6): δ (ppm): 8.78 (s, H, NH, inthlak danglam theih), 9.14 (s, 1H, CH=), 7.36-8.55 (m, 13H, heteroaromatization) C23H15N3O (348.38) atana chhut chhuah: C, 79.07; H, 4.33 a ni a; N, 12.03 a ni. Hmuhchhuah: C, 78.93; H, 3.97 a ni a; N, 12.36% a ni.
Compound 4 (2 mmol, 0.7 g) chu dry dioxane 20 ml (triethylamine drop tlemte leh thiourea/semicarbazide 2 mmol awmna)-ah a hmin a, reflux hnuaiah 2 h chhung a lum a. Solvent chu vacuum-ah a hmin a. Residue chu dioxane atang chuan recrystallized in mixture a awm ta a ni.