Moxifloxacin/Gatifloxacin‐1,2,3‐triazole‐isatin Hybrids with Hydrogen‐Bond Donor and Their In Vitro Anticancer Activity

A series of novel moxifloxacin/gatifloxacin‐1,2,3‐triazole‐isatin hybrids ( 8a – i ) were designed, synthesized, and screened for their in vitro anticancer activity in this paper. All of the synthesized hybrids were active against A549 and HepG2 cancer cell lines, whereas the parent drugs moxifloxacin and gatifloxacin were devoid of activity. Among them, hybrid 8i (IC₅₀: 41.1–98.3 μM) showed considerable activity against A549, HepG2, and MCF‐7 cancer cell lines, and it was no inferior to Vorinostat (IC₅₀: 64.32 to >100 μM) against the three cancer cell lines. Thus, this kind of hybrids has potentiality for discovery of new anticancer candidates for clinical deployment in the control and eradication of cancers.     

Synthesis of Substituted Quinolinyl Ether‐based Inhibitors of PI3K as Potential Anticancer Agents

A new strategy for the preparation of 8‐quinolyl ethers 3 ( a – g ), 5 ( a – g ), and 7 ( a – d ) was studied by copper (II)‐catalyzed methodology in the presence of Cs₂CO₃ and acetone–water mixture (1:1). Screening of quinolinyl‐8‐ethers was investigated against anticancer expressive studies to validate new chemical entity in medicinal chemistry. Approaches were evaluated against breast cancer (MCF‐7), skin cancer (G‐361), and colon cancer (HCT 116) cell lines. Inhibitory potentials against phosphoinositide‐3‐kinase (PI3K) enzyme responsible for cancer development have been evaluated by competitive ELISA studies. In PI3K assay, 3a – c were inactive (IC₅₀ > 5 μM), while 3e – g , 5a , 5c – e , 5g , 7a , and 7d showed a moderate activity (IC₅₀ ≥ 0.05 μM). Compounds ( 5b , 5f , 7b , and 7c ) showed significant activity (IC₅₀ < 1.0 μM); thus, their anticancer activities were carried out. Anticancer activity was found to be selective towards breast cancer (MCF‐7); 5b , 5f , 7b , and 7c showed predominant relative percentage activities of 74.12%, 79.04%, 72.56%, and 78.47%, with IC₅₀ values of 5b (2.27 ± 0.88 μM), 5f (1.38 ± 0.60 μM), 7b (2.64 ± 0.86 μM), and 7c (1.87 ± 0.68 μM) compared with the standard doxorubicin 73.14% inhibition (IC₅₀ = 1.98 ± 0.75 μM). Docking study also conducted to find out the binding interactions with p110α (PDB ID: 3T8M) enzyme. Compounds 5b , 5f , 7b , and 7c showed best docking score into the active site of PI3K 12.59, 10.51, 56.52, and 8.61 nM. Structure–activity relationship studies demonstrated that the synthesized compounds are the potential PI3K inhibitors to treat various cancer‐related diseases.     

Ciprofloxacin/Gatifloxacin‐1,2,3‐triazole‐isatin Hybrids and Their In Vitro Anticancer Activity

Eleven novel ciprofloxacin/gatifloxacin‐1,2,3‐triazole‐isatin hybrids ( 8a – k ) were designed, synthesized, and screened for their in vitro anticancer activity in this paper. A significant part of the synthesized hybrids was active against A549, HepG2, and SF‐268 cancer cell lines, whereas the parent drugs ciprofloxacin and gatifloxacin were devoid of activity. Among them, hybrid 8i (IC₅₀: 78.1–90.7 μM) was found to be the most active against A549, HepG2, and SF‐268 cancer cell lines, and it was comparable with or better than Vorinostat (IC₅₀: 71.1 to >100 μM). Thus, these kind hybrids have potentiality for discovery of new anticancer candidates for clinical deployment in the control and eradication of cancers.     

Design,Synthesis, and Anticancer Activity of 3H–benzo[f]chromen‐3‐one Derivatives

A series of substituted aminomethylbenzocoumarin derivatives 8a–i have been synthesized, characterized, and structure of compound 8g was confirmed by X‐ray single crystal analysis. All the synthesized compounds were tested for their anticancer activity against cancer cell lines A549 (lung carcinoma cell line), MCF7 (breast cancer cell line), and A375 (melanoma cell line). Compounds 8a , 8f , and 8h showed excellent growth inhibitory activity against all three cell lines, respectively. Compounds 8a and 8f were also found to be quite promising at very low concentration as an anticancer agent against MCF7 and A549 cell lines. Compounds 8g and 8i showed excellent antimitotic activity with IC₅₀ 0.32 and19.98 nM for A549 cell line.     

Synthesis and Ameliorative Effect of Isatin–Mesalamine Conjugates on Acetic Acid‐induced Colitis in Rats

A series of new isatin–mesalamine conjugates ( 9a – g ) were synthesized via conjugation of isatin ( 3a ) and its derivatives ( 3b – 3d , 4 , 5 , and 6 ) with mesalamine ( 7 ) by using chloroacetyl chloride as a bifunctional linker. Compounds 3a – 3d were prepared by employing Sandmeyer reaction. Compounds 4 , 5 , and 6 were obtained from isatin ( 3a ) via previously reported methods. The synthesized compounds were characterized by IR, mass, ¹H NMR, and ¹³C NMR spectral techniques. Synthesized compounds ( 3a – d , 4 , 5 , 6 , and 9a – g ) were evaluated for in vitro antioxidant activity by DPPH assay method using ascorbic acid as standard. Hybrids 9b (IC₅₀ = 368.6 ± 3.5 μM) and 9f (IC₅₀ = 335.1 ± 2.9 μM) showed better antioxidant activity than its parent compounds such as 3a (IC₅₀ = 556.8 ± 2.9 μM), 5 (IC₅₀ = 511.9 ± 3.6 μM), and 7 (IC₅₀ = 768.9 ± 2.7 μM). Acetic acid‐induced ulcerative colitis in rat model was chosen to examine the antioxidant potential of the synthesized hybrids ( 9b and 9f ) in the amelioration of ulcerative colitis. Colonic myeloperoxidase and malondialdehyde enzymes were used as biomarkers of anti‐ulcerative colitis activity. In the present study, hybrids 9b and 9f reduced the levels of colonic myeloperoxidase and malondialdehyde enzymes significantly (p < 0.05) when compared with control (colitic), at a dose (0.03 mM/12.5 mg/kg b.w. p.o.) (50%) less than that of its parent moieties mesalamine (0.16 mM/25 mg/kg) and isatin (0.16 mM/25 mg/kg). Thus, the molecular hybridization was proved to be significant in enhancing the activity of hybrids 9b and 9f by reducing the dose.     

Synthesis,biological evaluation and molecular docking studies of novel 2-(2-cyanophenyl)-N-phenylacetamide derivatives

A series of novel 2-(2-cyanophenyl)-N-phenylacetamide derivatives 3(a-u) were designed and synthesized via selective amidation of methyl-2-(2-cyanophenyl)acetates over amidine formation by using AlMe₃ as catalyst in good yields. All the newly synthesized derivatives were well characterized by ¹H NMR, ¹³C NMR, FTIR and HRMS spectral techniques. All the synthesized title compounds were evaluated for their in vitro anticancer activity against three cancer cell lines. Among all compounds, 3i (IC₅₀?=?1.20 μM, IC₅₀?=?1.10 μM), 3j (IC₅₀?=?0.11 μM, IC₅₀?=?0.18 μM), 3o (IC₅₀?=?0.98 μM, IC₅₀?=?2.76 μM) showed excellent inhibitory activity than the standard Etoposide (IC₅₀?=?2.11 μM, IC₅₀?=?3.08 μM) against MCF-7 and A-549 cell lines, respectively. Docking analysis of all the compounds with the human topoisomerase II revealed that the compound 3j fitted well in the active site pocket, showing the best docking score of 158.072 kcal/mol.

     

Et3N‐Prompted Efficient Synthesis of Anthracenyl Pyrazolines and Their Cytotoxicity Evaluation against Cancer Cell Lines

A series of anthracenyl pyrazoline derivatives ( 3a – o ) were synthesized with an aim to evaluate their in vitro anticancer activities. Anthracenyl pyrazoline compounds were prepared by the reaction between various anthracenyl chalcones ( 1a – o ) and hydrazine hydrate ( 2 ). The reactions were carried out under reflux in the presence of triethylamine and ethanol for 24 h, and the obtained yields were from good to excellent (90–97%). The structure of each compound is well characterized by IR, ¹H‐NMR, ¹³C‐NMR, elemental analyses, and mass spectroscopic technics, and the molecular structures of compounds 3d and 3e were solved by single‐crystal X‐ray crystallographic methods. The newly synthesized compounds ( 3a – o ) were evaluated for their in vitro cytotoxic studies against four human cancer cell lines MCF‐7 (breast cancer cell lines), SK‐N‐SH (neuroblastoma cancer cell lines), HeLa (cervical cancer cell lines), and HepG2 (liver cancer cell lines), and the screening results show strong cytotoxic effects for most of the synthesized compounds against the three cell lines except SK‐N‐SH cells. Notably, compounds 3a , 3j , 3l , 3m , 3n , and 3o showed a highly potential activity against HeLa cells (IC₅₀: 0.22, 0.3, 0.3, 0.10, 0.25, and 0.25 μM), while compounds 3i , 3k , 3l , and 3m showed a significant cytotoxic activity in HepG2 cells (IC₅₀: 0.22, 0.44, 0.40, and 0.22 μM), whereas compounds 3a , 3b , 3d , and 3e exhibit a promising cytotoxicity against MCF‐7 cells (IC₅₀: 0.73, 0.495, 0.493, and 0.66 μM).     

Design,synthesis, anticancer activity,and in silico studies of novel imidazo[1,2-a]pyridine based 1H-1,2,3-triazole derivatives

A novel series of imidazo[1,2-a]pyridine based 1H-1,2,3-triazole derivatives were designed, synthesized, and evaluated for their anticancer activity against two different human cancer cell lines. Most of the synthesized compounds displayed anticancer activity with IC₅₀ values from 2.35 to 120.46 μM. Furthermore, compounds 9b , 9c, 9d, 9f , and 9j showed potent inhibitory activity against cancer cell lines, with IC₅₀ values close to that of standard drug. It is important to note that compound 9d was more potent than the standard drug cisplatin with IC₅₀ values of 10.89 and 2.35 μM against Hela cell line and MCF-7 cell line, respectively.     

Synthesis and Anticancer Evaluation of Some Novel 5‐Amino[1,2,4]Triazole Derivatives

Novel [1,2,4]triazole derivatives were synthesized via various synthetic pathways. Among which were different substituted [1,2,4]triazole analogues that were synthesized, in addition to various fused [1,2,4]triazolo[1,5‐a]pyrimidine derivatives, [1,2,4]triazolo[1,5‐a][1,3,5]triazines, and [1,2,4]triazolo[5,1‐c][1,2,4]triazines. Besides, benzo[h][1,2,4]triazolo[5,1‐b]quinazolines, [1,2,4]triazolo‐[5,1‐b]quinazoline, [1,2,4]triazolo[1,5‐a]quinazoline and [1,2,4]triazolo[5,1‐d][1,2,3,5]tetrazine derivatives were also synthesized. The newly synthesized compounds were evaluated for their in vitro anticancer activity against liver cancer HepG2 and breast cancer MCF7 cell lines compared with the reference drug doxorubicin. Compounds 4 , 7 , 15 , 17 , 28 , 34 , and 47 were found to exert promising anticancer activity against HepG2 cell line showing IC₅₀ values ranging from 17.69 to 25.4 μM/L, while compounds 7 , 14a , 17 , 28 , and 34 showed significant activity against MCF7 cell line with IC₅₀ values ranging from 17.69 to 27.09 μM/L.     

Synthesis and antitumor evaluation of some new derivatives and fused heterocyclic compounds derived from thieno[2,3-b]pyridine: Part 2

As a continuation of our research on developing anticancer agents and based on the proven proprieties of thieno[2,3-b]pyridines as anticancer, we have designed to synthesize novel thieno[2,3-b]pyridine derivatives that incorporate different biologically active heterocycles through various chemical reactions. All of the newly obtained compounds, compared with the standard anticancer drug (doxorubicin), were screened in vitro for their antitumor activity against hepatocellular carcinoma (HepG-2) and human breast cancer (MCF-7) cell lines. The results revealed that compounds 3 , 7 , 12 , and 19 were found to be the most potent against both HepG-2 and MCF-7 cell lines exhibiting IC₅₀ values ranging from 3.67 to 11.50 and 5.13 to 11.80 μg/mL, respectively, among which compound 7 has a more potent activity than the reference drug doxorubicin against HepG-2 cell line, showing IC₅₀ value of 3.67 μg/mL (doxorubicin 4.65 μg/mL).     

The anti-lung cancer activity of propylene tethered dihydroartemisinin-isatin hybrids

Nineteen propylene tethered dihydroartemisinin-isatin hybrids 5a-g and 6a-l were designed, synthesized, and screened for their in vitro antiproliferative activity against three lung cancer cell lines, inclusive of drug-sensitive (A549), doxorubicin-resistant A549 (A549/DOX) and cisplatin-resistant A549 (A549/DDP) cell lines. The cytotoxicity of the synthesized hybrids towards normal lung epithelial cell line (BEAS-2B) was also assessed to evaluate the selectivity. The structure-activity relationship (SAR) elucidated that (1) alkyloxylimino fragment at C-3 position of isatin moiety were more favorable than the carbonyl and benzoxylimino, and the relative contricution order was methoxylimino > ethoxylimino > carbonyl > benzoxylimino; halogen atom at C-5 or C-6 position of isatin fragment could enhance the activity. Among them, hybrid 6f (IC₅₀: 21.7–28.9 μM) showed promising activity against the three tested lung cancer cell lines, and the activity was not inferior to that of cisplatin (IC₅₀: 19.7 and 66.9 μM) and doxorubicin (IC₅₀: 54.3 and 15.1 μM) against multidrug-resistant A549/DOX and A549/DDP lung cancer cell lines. In addition, hybrid 6f (IC₅₀: >100 μM) was non-cytotoxic towards normal lung epithelial cell line (BEAS-2B), and the RI values of hybrid 6f were 1.12 and 1.33. Further, hybrid 6f also possessed acceptable stability in mouse and human microsomes. Accordingly, hybrid 6a was a promising anti-lung cancer chemotherapeutic candidate and merited further evaluations.     

Design,synthesis, and anticancer evaluation of acetamide and hydrazine analogues of pyrimidine

A library of acetamide and hydrazine analogues were generated on the pyrimidine ring through a multistep reaction starting from 5-nitro-pyrimidine-4,6-diol and pyrimidine-4,6-diol, respectively. The synthesized analogues were screened for in vitro cytotoxic activity against various human cancer cell lines like HCT-1 and HT-15 (colon), MCF-7(breast), PC-3 (prostrate), SF268 (CNS) using MTT method. From the bioassay results, it was observed that even though many of the synthesized derivatives exhibited a good potency against various screened cancer cell lines, compound 14a from the acetamide series was found to show potent anticancer activity on all the tested cancer cell lines with IC₅₀ value of 0.36μM on CNS cell line and 1.6μM on HT-21 cell line, and compound 19xxi from hydrazine series of pyrimidine showed potent activity against three tested cancer cell lines with IC₅₀ value of 0.76μM on HT-29 cell line, 2.6μM on HCT-15, and 3.2μM on MCF-7 cell line.     

Design and synthesis of novel 7-[(N-substituted-thioureidopiperazinyl)-methyl]-camptothecin derivatives as potential cytotoxic agents

Abstract

As part of continuing our research on diverse C-7 derivatives of camptothecin (CPT), 16 CPT derivatives bearing piperazinyl-thiourea chemical scaffold and different substituent groups have been designed, synthesized and evaluated in vitro for cytotoxicity against five tumor cell lines (A-549, MDA-MB-231, MCF-7, KB and KBvin). As a result, all the synthesized compounds showed promising in vitro cytotoxic activity against the five tumor cell lines tested, and were more potent than irinotecan. Importantly, compounds 13?g (IC₅₀ = 0.514?μM) and 13o (IC₅₀ = 0.275?μM) possessed similar or better antiproliferative activity against the multidrug-resistant (MDR) KBvin subline than that of topotecan (IC₅₀ = 0.511?μM) and merit further development as anticancer candidates for clinical trail. With these results in hand, we have a reason to conclude that incorporating piperazinyl-thiourea motifs into position-7 of camptothecin confers well cytotoxic activity against cancer cell lines, probably resulting in new anticancer drugs.     

Design,Synthesis, and Biological Evaluation of 2‐(4‐Aminophenyl)benzothiazole Analogues as Antiproliferative Agents

A series of 28 novel 2‐(4‐aminophenyl)benzothiazole analogues have been synthesized and characterized using various analytical techniques like ¹H NMR, ¹³C NMR, electrospray ionization mass spectrometry, and IR and bioevaluated for their antiproliferative activity over a group of three human cancer cell lines, namely, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MDA‐MB‐231), using sulforhodamine B assay method. Few synthesized molecules ( 5a , 5c , 5d , 5f , 7b , and 7j ) displayed effective growth inhibition (GI₅₀) activity against the tested human cancer cell lines at lower micromolar concentration (GI₅₀) values in the range 0.2–1.7 μM. Noticeably, compound 7b exhibited reasonable activity in all three cancer cell lines in the GI₅₀ range 0.55–1.2 μM. Further, when 7b was screened for tubulin polymerization inhibition, it exhibited more than 55% inhibition at concentration of 5.0 μM. The molecular docking simulations supported the molecular interactions of the derivatives with the targeted receptor. These derivatives may serve as lead structures for development of potential anticancer drug candidates, and 7b might act as a potential microtubule polymerization inhibitor.     

Effect of lipophilicity of wingtip groups on the anticancer potential of mono N‐heterocyclic carbene silver(I) complexes: Synthesis,crystal structures and in vitro anticancer study

A series of symmetrically n ‐alkyl‐substituted mono benzimidazolium salts with steady increase in n ‐alkyl chain length have been prepared by stepwise N ‐alkylation resulting in salts ( 1 – 8 ). The mono N‐heterocyclic carbene (NHC)–Ag(I) complexes ( 9 – 16 ) derived from the respective salts were readily accessible by in situ deprotonation using Ag₂O. All the salts and the complexes were characterized using Fourier transform infrared, ¹H NMR, ¹³C NMR and elemental analyses. Furthermore, the structures of salts 3 and 7 and complex 16 were elucidated using X‐ray crystallography, which established that this mono NHC–Ag(I) complex has a linear bis‐carbene arrangement (C₂–Ag). The proligands and the respective Ag(I) complexes were studied for their in vitro anticancer potential against human colon cancer cell line (HCT‐116) using 5‐fluorouracil as a standard. From the IC₅₀ values of all the tested compounds, it can be postulated that there is an influential relationship between the increase in chain length of the wingtip n ‐alkyl groups and the anticancer potential. The proligands 4 – 8 and their respective complexes 12 – 16 with long n ‐alkyl chain lengths (n  = 6–10) showed better IC₅₀ values (0.3–3.9 μM) than the standard drug with the complexes displaying markedly better antiproliferation activity against HCT‐116 cell line than the respective proligands and the standard drug (IC₅₀ = 10.2 μM).     

Synthesis,anticancer evaluation,and molecular modeling study of new 2-(phenylamino)pyrazolo[1,5-a]pyrimidine analogues

The reaction of 3-amino-5-phenylaminopyrazoles 2 with 3-(dimethylamino) acrylonitrile derivatives resulted in a series of substituted pyrazolopyrimidine analogues 4 and 6. The DFT studies of the isolated compounds showed that the frontier molecular orbitals energy gap was close and in the 2.65–2.81 eV range where the derivative 6b has the lowest and both of 4a and 4c have the highest values. Meanwhile, the anticancer activity of the newly synthesized pyrazolopyrimidine analogues have been tested against several different cell lines (MCF-7, PC3, Hep-2 and WI38). The investigated pyrazolopyrimidines showed remarkable cytotoxicity activity against the MCF-7 and Hep-2 cell lines. In comparison to the effects of 5-fluorouracil, IC₅₀ = 10.19 ± 0.42 and 7.19 ± 0.47, compounds 6a-c demonstrated potential anticancer activity with IC₅₀ values for MCF-7 (10.80 ± 0.36–19.84 ± 0.49 μM) and Hep-2 (8.85 ± 0.24–12.76 ± 0.16 μM). Important details regarding the protein's binding sites were disclosed when the produced analogues docked with the crystal structure of the KDM5A protein, which was located in the protein data library.     

Ciprofloxacin‐isatin‐1H‐1,2,3‐triazole Hybrids: Design,Synthesis, and in vitro Anti‐tubercular Activity against M. tuberculosis

A new set of ciprofloxacin (CPFX)‐isatin‐1H‐1,2,3‐triazole hybrids 6a – l with greater lipophilicity compared with the parent CPFX was designed, synthesized, and assessed for their in vitro anti‐mycobacterial activity against Mycobacterium tuberculosis (MTB) H₃₇Rv as well as cytotoxicity in VERO cell line. The preliminary results showed that all hybrids (MIC: 0.39–50 μg/mL) exhibited promising activities against MTB H₃₇Rv, and six of them (MIC: 0.39–1.56 μg/mL) were more active than the parent CPFX (MIC: 3.12 μg/mL). In particular, the most active conjugate 6h (MIC: 0.39 μg/mL) was comparable with RIF (MIC: 0.39 μg/mL), and eight times more potent than CPFX. All conjugates (CC₅₀: 4–64 μg/mL) were more toxic than the parent (CC₅₀: 128 μg/mL) in VERO cell lines, and the most active hybrids, which also displayed the highest cytotoxicity, should be further optimized.     

Synthesis,characterization and biological evaluation of some novel sulfonylthiosemicarbazides

Abstract

A series of thiosemicarbazides were synthesized and structurally characterized by spectroscopic techniques (NMR, FT-IR) besides elemental analysis. These compounds were evaluated for their cytotoxicity against human breast cancer cell line MCF7 and prostate cancer cell line PC3 and nonmalignant fibroblast L929 cell line by MTT assay. Among the compounds, N-[2-(4-chlorophenyl)ethyl]-2-[(4-methylphenyl)sulfonyl]hydrazinecarbothioamide (3d) and 2-[(4-methylphenyl)sulfonyl]-N-[4-(trifluoromethoxy)phenyl]hydrazinecarbothioamide (3f) were found to display significant cytotoxicity with IC₅₀ of 13.87?μM (against PC3 cell line) and 1.47?μM (against MCF7 cell line), respectively. These compounds were non-cytotoxic to normal cell line with IC₅₀>100?μM. Western blotting studies demonstrated that compound 3f induced apoptosis and caused cell death in the MCF7 and PC3 cell lines via an increase in Bax protein expression and a slight decrease in Bcl-2 protein expression. The gene expression ratio Bax/Bcl-2 showed the induction of mitochondrial apoptosis in cancer cell lines. All of synthesized compounds have also been tested for antioxidant activity and all compounds achieved strong inhibition of the DPPH radical. These findings showed that compound 3f, displays potential to be further explored in the development of new anticancer agents.     

Design,synthesis and docking studies of new hydrazinyl-thiazole derivatives as anticancer and antimicrobial agents

Increase in the number of infections caused by pathogenic microbes in cancer patients has prompted the searcher to invest in the development of agents having dual anticancer and antimicrobial properties. The present study is concerned with synthesis and screening for anticancer and antimicrobial activity of a series of 5-hydrazinyl-2-(2-(1-(thien-2-yl)ethylidene)hydrazinyl)thiazole derivatives. The structure elucidation of the synthesized hydrazinyl thiazole derivatives was illustrated by spectroscopic and elemental analysis. All the newly synthesized compounds 5a-p were evaluated for in-vitro cytotoxic activity against breast carcinoma (MCF-7 cell line), hepatocellular carcinoma (HePG-2) and colorectal cancer (HCT-116) cell lines using MTT assay method. Compounds 5 g, 5h showed broad spectrum activity against three cancer cell lines with IC₅₀ ranged from 3.81 to 11.34 µM in compared to the reference drug Roscovitine (IC₅₀ = 9.32 to 13.82 µM), while compounds 5 l and 5 m were found to be more selective against HePG-2 and HCT-116 cell line (IC₅₀ = 9.29 and 8.93 µM respectively) and compound 5j was more selective against HePG-2 and MCF-7 cell lines (IC₅₀ = 6.73 and 10.87 µM respectively). The inhibitory activity of the most promising compounds was tested against the EGFR and ARO enzymes and were further tested for apoptosis and Annexin V/PI staining. The results of enzyme-based tests revealed that the tested compound 5j has a dual inhibitory effect on the EGFR and ARO enzymes with IC₅₀ = 82.8 and 98.6 nM respectively in compared to the reference drugs Erlotinib and Letrozole (IC₅₀ = 62.4 and 79 nM respectively). Furthermore, the majority of the tested hydrazinyl thiazole derivatives exhibited significant antimicrobial activity against the used pathogenic microbes species. Compounds 4b, 5h, 5j and 5 m exerted a good antibacterial and antifungal activity against all tested pathogenic microbes. Therefore, it was concluded that compounds 5 h, 5j and 5 m proved to possess dual anticancer and antimicrobial agent and may serves as a useful lead compounds in search for further modification or derivatization to give more potent and selective agents.     

Design,synthesis and molecular modeling studies of few chalcone analogues of benzimidazole for epidermal growth factor receptor inhibitor in search of useful anticancer agent

In the present investigation, few 3-(substitutedphenyl)-1-[2-(1-hydroxy-ethyl)]-1H-benzimidazol-1-yl)prop-2-en-1-ones are EGFR antagonist are designed, by molecular docking analysis. The synthesized compounds were tested for their in vitro anticancer activity by propidium iodide fluorescent assay and Trypan blue viability assay against colorectal cancer cell lines (HCT116) and non-small cell lung cancer cell lines (H460). Human Epithelial Kidney cell lines (HEK) are used as normal cell lines for studying effect of drug on non-cancerous cells within human body. Evaluation of cytotoxic studies of synthesized compounds CHL(1–8) reveal that compound CHL1 [IC₅₀ = 7.31 and 10.16 μM against HCT116 and H460 cell lines respectively, by PI assay] and CHL8 [IC₅₀ = 12.52 and 6.83 against HCT116 and H460 μM cell lines respectively] possess promising cytotoxic activity.