A new one-parameter lifetime distribution and its regression model with applications.

Lifetime distributions are an important statistical tools to model the different characteristics of lifetime data sets. The statistical literature contains very sophisticated distributions to analyze these kind of data sets. However, these distributions have many parameters which cause a problem in estimation step. To open a new opportunity in modeling these kind of data sets, we propose a new extension of half-logistic distribution by using the odd Lindley-G family of distributions. The proposed distribution has only one parameter and simple mathematical forms. The statistical properties of the proposed distributions, including complete and incomplete moments, quantile function and Rényi entropy, are studied in detail. The unknown model parameter is estimated by using the different estimation methods, namely, maximum likelihood, least square, weighted least square and Cramer-von Mises. The extensive simulation study is given to compare the finite sample performance of parameter estimation methods based on the complete and progressive Type-II censored samples. Additionally, a new log-location-scale regression model is introduced based on a new distribution. The residual analysis of a new regression model is given comprehensively. To convince the readers in favour of the proposed distribution, three real data sets are analyzed and compared with competitive models. Empirical findings show that the proposed one-parameter lifetime distribution produces better results than the other extensions of half-logistic distribution

Synthesis and biological activities of new bis-indole derivatives via microwave irradiation

Halawa AH, Bedair AH, El-Agrody AM, et al. Synthesis and biological activities of new bis-indole derivatives via microwave irradiation. Zeitschrift für Naturforschung B. 2017;72(9):639-646.Three new series of bis-indole derivatives were synthesized based on p-phenylenediamine (2-4, 5 and 6) and 4,4'-ethylenedianiline moieties (7-9) using facile and efficient condensation of three positional isomeric indole-carboxaldehyde derivatives (1a-c) with bifunctional amines upon microwave irradiation. The symmetric dimeric indole derivatives 2-4 as well as non-symmetric analogues 5 and 6 were obtained by in situ condensation of the respective positional 3-, 2- and 5-isomeric indole-carboxaldehydes with p-phenylenediamine, while compounds 7-9 resulted from respective condensation based on 4,4'-ethylenedianiline. Structures of the obtained compounds were deduced by advanced spectroscopic methods (H-1 NMR, C-13 NMR and MS). In agar diffusion assay, derivative 6 showed moderate antibacterial activity against various Gram positive and negative bacteria, while derivative 7 displayed moderate activity against several Gram positive bacteria. However, in Resazurin assay employing the human cervix carcinoma cell line (KB-3-1), derivatives 2-9 turned out to be inactive

Synthesis of diverse amide linked bis-indoles and indole derivatives bearing coumarin-based moiety: cytotoxicity and molecular docking investigations

Halawa AH, Abd El-Gilil SM, Bedair AH, et al. Synthesis of diverse amide linked bis-indoles and indole derivatives bearing coumarin-based moiety: cytotoxicity and molecular docking investigations. MEDICINAL CHEMISTRY RESEARCH. 2018;27(3):796-806.New amide linked bis-indoles 10a, b, and 12 have been synthesized by treatment of tryptamine (9) or 5-aminoindole (11) with oxalyl chloride or adipoyl chloride. In addition, a newly indole derivatives 14-16 incorporated or fused with coumarin moieties have been prepared through the reaction of 9 or 11 with 4-chloro-3-formylcoumarin (13a) or 4-chloro-3-nitrocoumarin (13b). Further, 13-(3-nitrophenyl)-6,13-dihydrochromeno[4,3-b]pyrrolo[3,2-f]quinolin-12(3H)-one (20) has been produced via one-pot Mannish reaction of 11, 4-hydroxycoumarin (17), and 3-nitrobenzaldehyde (18) in the presence of N-chlorosuccinimide (NCS) as a catalyst. A mixture of 3-[(3H-indol-3-ylidene)methyl]-4-hydroxy-2H-chromen-2-one (24A), and 3-[(1H-indol-3-yl)methylene]chroman-2,4-dione (24B) has been obtained with ratio 1:1 through Knoevenagel condensation reaction of indole-3-carboxaldehyde (21) and 17. Structures of the obtained compounds have been assigned by sophisticated spectroscopic techniques (H-1-NMR, C-13-NMR, and 2D NMR) and mass spectrometry. All the synthesized compounds have been screened for their cytotoxic activity against the human cervix carcinoma cell line (KB-3-1), where compounds 14a, 16, and 20 exhibit the highest potent activity (IC50 = 1.8, 2.2, and 7.9 A mu M, respectively) in comparison with the positive control (+)-Griseofulvin (IC50 = 19.2 A mu M), whereas the tautomeric mixture 24A, B show moderate activity (IC50 = 71.3 A mu M). Moreover, molecular docking study of the synthesized compounds toward the matrix metalloproteinase-8 (MMP-8) (PDB ID: 1MNC) has also discussed

Synthesis, biological activity and molecular modeling study of new Schiff bases incorporated with indole moiety

Halawa AH, Abd El-Gilil SM, Bedair AH, et al. Synthesis, biological activity and molecular modeling study of new Schiff bases incorporated with indole moiety. Zeitschrift für Naturforschung C. 2017;72(11-12):467-475.A new series of heterocyclic Schiff bases 2-9 containing indole moiety were synthesized by facile and efficient condensation of indole-3/2/5-carboxaldehyde (1a/1b/1c) with different aromatic and heterocyclic primary amines using conventional and/or microwave irradiation methods. The structures of the obtained compounds were assigned by sophisticated spectroscopic and spectrometric techniques (1D-NMR, 2D-NMR and MS). The synthesized compounds were screened for their cytotoxicity and antibacterial activities. In vitro cytotoxicity screening revealed that compound 5 exhibited moderate activity against KB-3-1 cell line (IC50 = 57.7 mu M) while 5-indolylimino derivative 7 indicated close to the activity (IC50 = 19.6 mu M) in comparison with the positive control (+)-Griseofulvin (IC50 = 19.2 mu M), while the tested compounds 5, 6b, 7 and 9 revealed good or moderate antibacterial activity. In addition, molecular docking study of Schiff bases 2-9 was performed by Molecular Operating Environment (MOE 2014.09) program on the matrix metalloproteinase-8 (MMP-8) (Protein Data Bank (PDB) ID: 1MNC) in an attempt to explore their mode of action as anticancer drugs

New bioactive compounds from the marine-derived actinomycete Nocardiopsis lucentensis sp. ASMR2

Eliwa EM, Abdel-Razek AS, Frese M, et al. New bioactive compounds from the marine-derived actinomycete Nocardiopsis lucentensis sp. ASMR2. Zeitschrift für Naturforschung B. 2017;72(5):351-360

Metal-free domino amination-Knoevenagel condensation approach to access new coumarins as potent nanomolar inhibitors of VEGFR-2 and EGFR

Eliwa EM, Frese M, Halawa AH, et al. Metal-free domino amination-Knoevenagel condensation approach to access new coumarins as potent nanomolar inhibitors of VEGFR-2 and EGFR. Green Chemistry Letters and Reviews. 2021;14(4):576-597.A metal-free, atom-economy and simple work-up domino amination-Knoevenagel condensation approach to construct new coumarin analogous (4a-f and 8a-e) was described. Further, new formyl (5a,d-f) and nitro (9a,d-f) coumarin derivatives were synthesized via C-N coupling reaction of various cyclic secondary amines and 4-chloro-3-(formyl-/nitro)coumarins (1a,c), respectively. The confirmed compounds were screened for their in vitro anti-proliferative activity against KB-3-1, A549 and PC3 human cancer cell lines using resazurin cellular-based assay. Among them, coumarin derivatives 4e and 8e displayed the best anti-cervical cancer potency (KB-3-1) with IC50 values of 15.5 ± 3.54 and 21 ± 4.24 µM, respectively. Also, 4e showed the most promising cytotoxicity toward A549 with IC50 value of 12.94 ± 1.51 µM. As well, 9d presented a more significant impact of potency against PC3 with IC50 7.31 ± 0.48 µM. Moreover, 8d manifested selectivity against PC3 (IC50 = 20.16 ± 0.07 µM), while 8e was selective toward KB-3-1 cell line (IC50 = 21 ± 4.24 µM). Matching with docking profile, the enzymatic assay divulged that 8e is a dual potent single-digit nanomolar inhibitor of VEGFR-2 and EGFR with IC50 values of 24.67 nM and 31.6 nM that were almost equipotent to sorafenib (31.08 nM) and erlotinib (26.79 nM), respectively

Synthesis, in vitro cytotoxicity activity against the human cervix carcinoma cell line and in silico computational predictions of new 4-arylamino-3-nitrocoumarin analogues

Halawa AH, Eliwa EM, Hassan AA, et al. Synthesis, in vitro cytotoxicity activity against the human cervix carcinoma cell line and in silico computational predictions of new 4-arylamino-3-nitrocoumarin analogues. JOURNAL OF MOLECULAR STRUCTURE. 2020;1200: UNSP 127047.A new series of 4-arylamino-3-nitrocoumarin analogues (4-18) have been synthesized and characterized by sophisticated spectroscopic techniques (H-1 NMR, C-13 NMR) and mass spectrometry. All the new synthesized compounds were evaluated for their in vitro cytotoxic activity against the human cervix carcinoma cell line (KB-3-1) using resazurin assay with (+)-griseofulvin as the positive control (IC50 = 19 mu M). Among them, thiazolidinylidene derivative 17a that bearing malononitrile unit displayed the best cytotoxic potency with IC50 value of 21 mu M. Also, in silico docking simulation studies were conducted on human DNA topoisomerase 1 (Top1) (PDB: 1T8I) to explore and interpret the interaction pattern between the selected compounds and target enzyme as well confirm the acquired cytotoxicity results. In addition to the above, in silico predictions of physicochemical properties, ADME (absorption, distribution, metabolism and excretion) parameters, oral toxicity and indication of toxicity targets were implemented for some title compounds. (C) 2019 Published by Elsevier B.V