Amin, K., O. El-Badry, D. Abdel-Rahman, and U. Ammar, "Synthesis and In Vitro Biological Evaluation of New Pyrido[2,3-b]pyrazinone-Based Cytotoxic Agents and Molecular Docking as BRAF Inhibitors", ChemistrySelect, vol. 4, pp. 8882 –8885, 2019. Abstract

In this study, synthesis of new pyrido[2,3-b]pyrazinone derivatives were identified. The in vitro cytotoxic activity of synthesized compounds against human colon cancer cell line (HCT 116) and kinase assay (V600EBRAF) were investigated. The results revealed that compounds 4b and 4c (4-nitro and 4-methoxybenzylidene acid hydrazide substitution, respectively) were the most active compounds among the synthesized derivatives (IC50 12.120 and 13.103 μM, respectively). Moreover, they exhibited inhibitory activity against V600EBRAF (Inh % 79.23 and 81.33, respectively). In addition, the designed derivatives were subjected to be simulated with the active site of mutated BRAF kinase domain using a suitable molecular docking protocol. Docking results coincided with good activity of compound 4c and showed high docking score with BRAF protein kinase domain -21.85171 kcal/mol better than native ligand. The results of this study consider pyridopyrazinone scaffold (with substituted phenyl ring through a spacer) a key nucleus for further molecular and structural optimization.

Hassan, G. S., D. E. Abdel-Rahman, E. A. Abdelmajeed, R. H. Refaey, A. M. Salem, and Y. M. Nissan, "New pyrazole derivatives: Synthesis, anti-inflammatory activity, cycloxygenase inhibition assay and evaluation of mPGES", Eur. J. Med. Chem., vol. 171, pp. 332-342, 2019. Abstract

New pyrazole derivatives 2e5 were synthesized and evaluated for their COX-1 and COX-2 inhibitory activity in vitro. All compounds showed good inhibitory activity at a nanomolar level and most compounds exhibited selectivity towards COX-2 inhibition. Compounds 2a, 3b, 4a, 5b and 5e exhibited IC50 towards COX-2 enzyme of 19.87, 39.43, 61.24, 38.73 and 39.14 nM, respectively. Furthermore, compounds 3b, 4a, 5b and 5e exhibited a selectivity index of 22.21, 14.35, 17.47 and 13.10, respectively. The most active compounds were further subjected to in vivo anti-inflammatory assay. The tested compounds showed better or comparable activity to celecoxib as positive control. In order to explore their binding mode and selectivity behaviour, molecular docking in the active site of COX-2 was carried out for these derivatives. Analysis of the docked poses of the compounds showed that they adopt similar conformations to the highly selective COX-2 inhibitor, SC-558. The docking pose of compound 3b was confirmed by molecular dynamics. All the tested compounds exhibited potent inhibitory effect on the production of PGE2, in addition to their inhibition of COX-2 enzyme.

El-Ansary, S. L., D. E. Abdel-Rahman, and L. M. A. Abdel-Ghany, "Synthesis and Anticancer Evaluation of Some New 3-Benzyl-4,8- Dimethylbenzopyrone Derivatives.", TOMCJ, vol. 11, pp. 81-91, 2017. Abstract

New benzopyrone derivatives such as Schiff’s like compounds, acetohydrazides or substituted with oxadiazole or pyrazole heterocycles were synthesized from parent acid hydrazide compound 3.
Methods and Materials:
Structures of the synthesized compounds were elucidated using IR, NMR and mass spectroscopy. All the synthesized derivatives were selected by National Cancer Institute (NCI), Bethesda, and evaluated for their in vitro anticancer activity in the full NCI 60 cell lines panel assay.
Results and Conclusion:
Schiffs like compounds 4a, b and c were found to have good growth inhibition % against numerous cell lines that belong mainly to leukemia, non-small cell lung, CNS and breast Cancer subpanels.

Hassan, G. S., D. E. Abdel-Rahman, Y. M. Nissan, E. A. Abdelmajeed, and T. M. Abdelghany, "Novel pyrazolopyrimidines: Synthesis, in vitro cytotoxic activity and mechanistic investigation.", Eur. J. Med. Chem., vol. 138, pp. 565 - 576, 2017. Abstract

A series of novel pyrazolo[3,4-d]pyrimidines bearing benzenesulfonamide moiety 5a-f, 6 and 7 were synthesized. Cytotoxic screening was conducted against MCF-7 and HepG2. 6-(4-Methoxyphenyl)-4-oxopyrazolopyrimidine derivative 5e and 4-imino-6-oxopyrazolopyrimidine derivative 6 revealed potent cytotoxic activity with IC50 1.4 µM (MCF-7) and 0.4 µM (HepG2), respectively compared to that of doxorubicin, (IC50 = 1.02 μM and 0.9 μM, respectively). Compounds 5e and 6 were subjected to cell cycle analysis and apoptosis assay after 24h and 48h treatment. Compound 5e arrested cell at G1 phase, while 6 arrested cell at S and G2/M phases, respectively. The apoptotic effect of both compounds were evidenced by pre G1 apoptosis as its percentage increased by time (7.38%, 11.61%) and (13.92%, 16.71%), respectively. Apoptosis induction capability was confirmed by the effect on early and late apoptosis and augmentation of caspase-3 level. Furthermore, compound 6 inhibited CDK2 enzyme with IC50 = 0.19 μM and increased levels of its regulators, P21 and P27 by 10.06% and 8.5%, respectively. Moreover, a molecular docking study of compound 6 on CDK2 enzyme was adopted to explore binding interaction with amino acid residues of its active site.

El-Ansary, S. L., D. E. Abdel-Rahman, and N. M. A. Eldydamony, "Coumarins: Biological activity and SAR studies.", Der Pharma Chemica,, vol. 8, issue 15, pp. 61-74, 2016. Abstract

Over the past decades, literature survey revealed that, many naturally occurring and synthetic coumarin derivatives have been discovered and biologically evaluated for a broad range and diverse biological activities. This review provides a systematic summary and insight of the whole range of medicinal chemistry in the current developments of coumarin compounds and some overview on photochemotharpy, linear (psoralen) and angular (angelicin) furocoumarins and structure-activity relationships are also discussed. The perspectives of the future development of coumarin based medicinal chemistry are also presented.

El-Ansary, S. L., G. S. Hassan, D. E. Abdel-Rahman, N. A. Farag, M. I. Hamed, and M. A. Baset, "Design, synthesis and biological evaluation of some new succinimide, 2-iminothiazoline and oxazine derivatives based benzopyrone as anticonvulsant agents.", Int. J. Pharm. Pharm. Sci., vol. 8, issue 4, pp. 222-228, 2016. Abstract

Objective: The objective of the present study was to synthesize novel benzopyrone derivatives with potential and safer anticonvulsant activity.
Methods: New benzopyrone derivatives have been synthesized and characterized by spectral and elemental analysis. These compounds tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens (phase 1), which are the most widely employed seizure models for early identification of new anticonvulsant agents. Phase 2 including, neurotoxicity screening and quantitative determination of the median effective dose (ED50), median lethal dose (LD50) and protective index (PI) for the active compounds from phase 1.
Results: Compound 12b possessed potent anticonvulsant activity with ED50 values of 94.75 and 70.7 mg/kg in the MES and scPTZ screens respectively, and had LD50 value of 2546 mg/kg after intraperitoneal injection to mice, which provide compound 12b with a wide protective index of 26.87 and 36.01 for MES and scPTZ screens respectively compared to the reference drug Phenobarbital with PI of 12.16 and 20.08, respectively. In addition, compound 12b exhibited mild neurotoxicity at the maximum administrated dose (200 mg/kg).
Conclusion: Compound 12b possessed broad spectrum activity for the treatment of all types of seizures, with a wide protective index compared to
Phenobarbital. Consequently, compound 12b can be selected as a new bio candidate lead for further study.

Amin, K. M., O. M. El-Badry, D. E. Abdel-Rahman, U. M. Ammar, and M. M. Abdallah, "Design, synthesis, anticancer evaluation and molecular docking of new V600EBRAF inhibitors derived from pyridopyrazinone.", Eur. J. Chem., vol. 7, issue 1, pp. 19-29 , 2016. Abstract

Design and synthesis of some new pyridopyrazinone derivatives as anti-proliferative agents were described. The cytotoxic activities of the synthesized compounds against melanoma cell line (LOXIMVI), ovarian cell line (OVCAR3), thyroid cell lines (CAL62, FTC133, BCPAP and ML1) and colon cell lines (HT29 and HCT116) were investigated. Results revealed that most compounds were active and compound 3d was the most active one. It exhibited promising activity against all tested cell lines. In addition, in vitro kinase assay against both WTBRAF and V600EBRAF was performed for all synthesized compounds. Furthermore, molecular docking of tested compounds was established with active site of V600EBRAF kinase domain. Results of kinase inhibition assay and molecular docking revealed that, compounds 1, 3d,e,h,I, 5d,e and 6b were potent inhibitors for V600EBRAF kinase enzyme involved in number of cancer types as melanoma, ovarian and thyroid cancer.

El-Ansary, S. L., D. E. Abdel-Rahman, and A. H. Abdel-Haleem, "Synthesis, antimicrobial, photochemotherapeutic evaluation and molecular docking of novel furobenzopyrones, tetrahydrobenzo- and benzofurobenzopyrones.", Der Pharma Chemica, vol. 6, issue 6, pp. 256 - 272, 2014. Abstract

New series of tricyclic compounds (linear furobenzopyrones 3a-d and angular furobenzopyrones 11a-h) and tetracyclic compounds (tetrahydrobenzofurobenzopyrone 5a,b and benzofurobenzopyrone 6a,b) derivatives were synthesized to ensure mono functional photoreaction with DNA in order to decrease toxicity. All prepared compounds were evaluated for antimicrobial and photochemotherapeutic activities. Compounds 2d, 3d, 5a, 10c and 11d were found to have good antimicrobial activity while only compound 11e exhibited good photosensitizing activity. In addition, molecular docking study was applied to elucidate a molecular target for the antimicrobial activity and gain insight into the possible binding mode of these compounds with the active site of the DNA gyrase.

El-Ansary, S. L., M. M. Hussein, D. E. Abdel-Rahman, and M. I. A. - L. Hamed, "New furobenzopyrones: Synthesis, antimicrobial and photochemotherapeutic evaluation, QSAR and molecular docking studies.", Der Pharma Chemica, vol. 6, issue 6, pp. 169 -191, 2014. Abstract

The synthesis of some new linear furobenzopyrone 3a-h, 7a,b and angular furobenzopyrone derivatives 9a-s and 12a,b were described on the base of being monofunctional compounds to decrease possible toxicity. All the prepared compounds were evaluated for their antimicrobial and photosensitizing activities. Compounds 2e, 4 and 7b were found to have good antimicrobial activity while only compound 2e exhibited higher photosensitizing activity than xanthotoxin. In addition, photosensitizing activity increased upon increasing time of radiation and concentration of substance. Quantitative structure–activity relationship (QSAR) study was applied to find a correlation between the photosensitizing activities of the newly synthesized furobenzopyrone derivatives and their physicochemical parameter. Furthermore, docking study was undertaken to gain insight into the possible binding mode of these compounds with the binding site of the DNA gyrase (topoisomerase II) enzyme which is responsible for resolving topological problems which arise during the various processes of DNA.

Abdel-Rahman, D. E., "Synthesis, Quantitative Structure–Activity relationship and biological evaluation of 1,3,4-oxadiazole derivatives possessing diphenylamine moiety as potential anticancer agents", Chem. Pharm. Bull. (Tokyo), vol. 61, issue 2, pp. 151 - 159, 2013. Abstract

Synthesis of 2,5-disubstituted-1,3,4-oxadiazole (2a–c), 3-substituted aminomethyl-5-substituted-1,3,4-oxadiazole-2(3H)-thione (4a–m) and 2-substituted thio-5-substituted-1,3,4-oxadiazole (5a, b) had been described. All the synthesized derivatives were screened for anticancer activity against HT29 and MCF7 cancer cell lines using Sulfo-Rodamine B (SRB) standard method. Most of the tested compounds exploited potent antiproliferative activity against HT29 cancer cell line rather than MCF7 cancer cell line. Compounds 2a–c, 4f and 5a exhibited potent cytotoxicity (IC50 1.3–2.0 μm) and selectivity against HT29 cancer cell line. Quantitative structure–activity relationship (QSAR) study was applied to find a correlation between the experimental antiproliferative activities of the newly synthesized oxadiazole derivatives with their physicochemical parameter and topological index.