Ahmed A. Al-Karmalawy

• Professor of Pharmacy
• Professor (Associate) at University of Mashreq

Herein, a series of N'-benzylidene-3,4-dimethoxybenzohydrazide derivatives were designed and synthesised to target the multidrug efflux pump (MATE). The antibacterial activities were screened against S. aureus, Acinetobacter, S. typhi, E. coli, and P. aeruginosa, whereas their antifungal activities were screened against C. albicans. Compounds 4a, 4...

Apparently, tubulin inhibitors binding to the colchicine-binding site (CBS) currently have outstanding attention for cancer treatment. So, a series of benzo[b]azonin-2-one derivatives having the same pharmacophoric features as colchicine binding site inhibitors (CBSIs) were synthesized targeting the CBS of β-tubulin. The antiprolifera-tive activiti...

The global outbreak of the COVID-19 pandemic provokes scientists to make a prompt development of new effective therapeutic interventions for the battle against SARS-CoV-2. A new series of N-(5-nitrothiazol-2-yl)-carboxamido derivatives were designed and synthesised based on the structural optimisation principle of the SARS-CoV Mpro co-crystallized...

Telomerase is an outstanding biological target for cancer treatment. BIBR1532 is a non-nucleoside selective telomerase inhibitor; however, it experiences ineligible pharmacokinetics. Herein, we aimed to design new BIBR1532-based analogues as promising telomerase inhibitors. Therefore, two novel series of pyridazine-linked to cyclopenta[b]thiophene...

Although the great effectiveness of doxorubicin (Dox) in the treatment of many types of tumors, it showed limited effectiveness against the head and neck squamous cell carcinoma (HNSCC) subtype which is attributed to its reported multiple drug resistance (MDR). In the current study, we considered the essential pharmacophoric features of Dox as an e...

Based on the rational design of DNA intercalators and Topo-II inhibitors and taking into consideration the main pharmacophoric features of doxorubicin (Dox) as a reference standard, we theoretically designed novel substituted tetrahydropyrimidine analogues (T1–35). The designed analogues (T1–35) were investigated for their inhibitory potential towa...

Herein, the antibacterial, antifungal and antiviral activities of Astragalus spinosus leaves, the largest genus in the family Fabaceae, were evaluated. Forty compounds were identified from the hydroalcoholic plant extract using the LCMS/MS technique. The identified candidates were chemically divided into hydroxycinnamic acid derivatives, flavonoids...

A method of treating cancer in a subject in need thereof includes administering to the subject a therapeutically effective amount of the compound of formula (I) or a pharmaceutically acceptable salt thereof, ##STR00001## where each of R.sub.1-R.sub.4, R.sub.5A-R.sub.7A, and R.sub.5B-R.sub.7B is independently selected from a hydrogen atom, a halogen...

A method of treating cancer that includes administering a therapeutically effective amount of an organoselenium benzimidazole compound of Formula (I), ##STR00001## where R is at least one selected from the group consisting of an alkyl group having 1 to 6 carbon atoms, an unsubstituted benzyl group, a para halo-substituted benzyl group, and an allyl...

Poly (ADP-ribose) polymerase (PARP) inhibitors have been authorized for the treatment of breast cancer (BC) and prostate cancer (PC). Recent studies suggest that inhibiting angiogenesis through the vascular endothelial growth factor receptor (VEGFR) enhances cellular sensitivity to PARP inhibitors. This study presents the design, synthesis and full...

CREBBP, CEBPA, and DNMT3A are tumor suppressor genes whose dysfunction has been reported in hematologic malignancies. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. We aim to assess the expression level of CREBBP, CEBPA, and DNMT3A genes in an Egyptian cohort with AML. We investigated the correlation between the s...

Clusiaceae comprises many biologically active plants. Among them, Clusia rosea Jacq. which possess antibacterial and anti‐HIV activities. In this study, the phytochemical constituents of Clusia rosea leaves methanolic extract was profiled using UPLC‐QTOF‐MS/MS. total phenolics and flavonoids content were determined. The antioxidant activity of the...

Chemical investigation of the ethyl acetate extract of the endophytic fungus Aspergillus terreus AArEF2 found in the fresh leaves of Artemisia arborescens L. led to isolation of five previously undescribed butenolides, asperterreunolides A-E (1-5), along with the known metabolite butyrolactone IV (6). The structure elucidation of these metabolites...

Osteoarthritis (OA) is a serious health issue that lacks a totally effective treatment. In light of the critical need for alternative therapies to halt osteoarthritis and its progress, This study explores the potential of Lolium perenne as a treatment for osteoarthritis for the first time. The research evaluates the plant's protective effects again...

A method for cytotoxically treating cancer cells includes contacting the cancer cells with a composition comprising a compound of Formula I. The compound of Formula I is contacted with the cancer cells in an amount effective to reduce the number of cancer cells by at least 50%. A method for preparing the compound of Formula I.

In oncology, pancreatic cancer (PC) continues to be a problem that requires creative approaches to therapy. This research aims to create dual kinase inhibitors that target VEGFR-2 and JNK-1, two important factors in the angiogenesis and progression of PC. We found compounds with promising anticancer action using phenyltriazolyl piperazine/(piperidi...

Herein, we report the design, synthesis, and characterization of novel organoselenium (OSe) hybrids (5–19) via modifications of the lead, N‐(4‐selaneylphenyl)‐2‐selaneylacetamide. The OSe‐based thiazol 9 showed the highest growth inhibition % (GI%) of 64.72% relative to the positive reference doxorubicin (DOX), with a GI% of 79.5%. Furthermore, the...

Cancer is causing about 8 million deaths each year. The EGFR plays a pivotal role in prompting cells to grow and survive, making it a major target for cancer treatment. Besides, STAT3 is essential for the development, growth, and maintenance of tumors. Moreover, multitarget-directed ligands can potentially offer better treatment results and improve...

New s‐triazine hydrazone hybrids (4a–4r) were designed and synthesized as promising microbial DNA gyrase inhibitors. This was done by taking the lead DNA gyrase inhibitor (AstraZeneca arylaminotriazine) as a reference. The novel samples were subsequently tested as antimicrobial agents against certain pathogenic bacteria and unicellular fungi. The a...

Selenium (Se)-based nanocomposites are promising compatible biomaterials as Se is a micronutrient trace element in our bodies and exhibits high sensitivity to anticancer activity and redox stimuli. Therefore, This work presents a low-cost strategy to develop novel materials based on TiO2/ZnO (ZT) organoselenium scaffolds possessing the diselenide (...

Alzheimer’s disease (AD) stands as one of the most outstanding progressive neurodegenerative disorders. Obviously, acetylcholine esterase (AChE) is the primary enzyme responsible for breaking down acetylcholine (ACh) with a much more prominent effect than butyrylcholine esterase (BuChE). Hence, novel quinazoline derivatives (3a-p) were designed and...

A method of treating cancer in a subject in need thereof includes administering to the subject a therapeutically effective amount of the compound of formula (I) or a pharmaceutically acceptable salt thereof, where each of R1-R4, R5A-R7A, and R5B-R7B is independently selected from a hydrogen atom, a halogen atom, a nitro group, a cyano group, a hydr...

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections represent critical global health challenges due to the high morbidity and mortality associated with co-infections. HIV, the causative agent of acquired immunodeficiency syndrome (AIDS), infects 4,000 people daily, potentially leading to 1.2 million new cases by 2025, while HC...

In this current work, we dedicated efforts to designing and synthesizing new 1,2,3-triazole-analogues (5a-d), (6a-d), and (7a-c) to act as dual VEGFR-2 and telomerase inhibitors with promising apoptotic potential. The synthesized analogues were examined against eleven diverse types of cancer cells and two normal cells to assess their ability to inh...

A method for cytotoxically treating cancer cells includes contacting the cancer cells with a composition comprising a compound of Formula I. The compound of Formula I is contacted with the cancer cells in an amount effective to reduce the number of cancer cells by at least 50%. A method for preparing the compound of Formula I.

Many plants are reported to enhance cognition in amnesic-animal models. The metabolite profile of Cordia dichotoma fruit methanolic extract (CDFME) was characterized by LC-QTOF-MS/MS, and its total phenolics content (TPC) and total flavonoids content (TFC) were determined. In parallel, its cognitive-enhancing effect on scopolamine (SCOP)-induced AD...

Many cancers have displayed resistance to chemotherapeutic drugs over the past few decades. EGFR has emerged as a leading target for cancer therapy via inhibiting tumor angiogenesis. Besides, studies strongly suggest that blocking telomerase activity could be an effective way to control the growth of certain cancer cells. Since multi-target design...

A zinc coordination organoselenium polymer may be a catalyst. The zinc coordination polymer may be a catalyst for biodiesel fuel. A method of forming biodiesel from waster oil may include using the zinc coordination polymer. The waste oil may be selected from a group consisting of vegetable oil and animal fats.

There is merit in investigating novel therapeutic molecules that hit vital targets during the viral infection cycle i.e. disrupting the interaction between SARS-CoV-2's spike glycoprotein and the host's angiotensin converting enzyme 2 (ACE2) receptor, potentially offering new avenues for treatment. Accordingly, lipid-based vesicular systems like li...

Thymus vulgaris is a highly regarded herb known for its wide medicinal and culinary uses. Endophytic fungi, residing harmlessly within plant tissues, have attracted much attention as potential sources of novel bioactive compounds. This study aimed to evaluate the chemical and biological characteristics of Alternaria alternata as an endophytic fungu...

A method for cytotoxically treating cancer cells includes contacting the cancer cells with a composition comprising a compound of Formula I. The compound of Formula I is contacted with the cancer cells in an amount effective to reduce the number of cancer cells by at least 50%. A method for preparing the compound of Formula I is also described.

Background: Endophytic fungi are known to produce bioactive compounds with potential therapeutic applications. Objective: This study investigated the antimicrobial and cytotoxic activities of Nigrospora oryzae, an endophytic fungus, isolated from Moringa oleifera. Methodology: Nigrospora oryzae was cultured, and its secondary metabolites were extra...

Organoselenium (OSe) compounds and Schiff bases have recently attracted prominent attention due to their promising anti-inflammatory activities. Herein, we disclose the anti-inflammatory properties of OSe tethered Schiff bases 3a-3c and 5a-5c synthesized starting from diaminodiphenyl diselenide (2). The anti-inflammatory potential of the target com...

This study examines Dabigatran’s (Dab) capacity to mitigate methotrexate (MTX)-induced coagulation disorders and endothelial dysfunction, while exploring its effects on oxidative stress and inflammatory pathways (NF-kB/IL-1β/MCP-1, TLR4/NLRP3) in reducing hepatotoxicity. Rats were assigned to four groups: a control group receiving saline intraperit...

Staphylococcus aureus (S. aureus) is a prominent infectious etiological agent in humans, dairy animals, and camels. Camel milk has all the nutrients which are nutritious and advantageous to the growth of S. aureus that dominates most bacterial species. So, the present work was designed to investigate the effect of certain toxin gene of S. aureus ba...

In this study, we designed and synthesized novel analogues of roflumilast that exhibit selective inhibition of PDE-4B. To accomplish this target; synthesis of novel series (4a-u, 5a-i, and 6) was done, aiming at obtaining new PDE-4B inhibitors hits based on the proposed pharmacophore, 1-(cyclopropylmethoxy)-2-(difluoromethoxy) benzene moiety. Enzym...

The SARS-CoV-2 main protease (Mpro) was introduced as a very promising target for various drug development processes. An orally active antiviral drug (PF-07321332) was developed by Pfizer as a Mpro inhibitor and approved as Nirmatrelvir. Nirmatrelvir is not administered alone due to its poor pharmacokinetic properties and is co-administered with Ri...

A method for cytotoxically treating cancer cells includes contacting the cancer cells with a composition comprising a compound of Formula I. The compound of Formula I is contacted with the cancer cells in an amount effective to reduce the number of cancer cells by at least 50%. A method for preparing the compound of Formula I

Inflammation is a complex process with many contributing factors, and it often causes pain. The pathophysiology of pain involves the release of inflammatory mediators that initiate pain sensation, as well as edema and other inflammation hallmarks. Selenium-containing compounds (OSe) are very promising for developing new medicines because they can t...

In this work, additional effort was applied to design new BIBR1532-based analogues with potential inhibitory activity against telomerase and acting as multitarget antitumor candidates to overcome the resistance problem. Therefore, novel substituted N-phenyl-2-((6-phenylpyridazin-3-yl)thio)acetamide candidates (4a-n) were synthesized. Applying the l...

Sulfonamides are promising classical carbonic anhydrase (CA; EC 4.2.1.1) inhibitors, being used for several medical purposes such as diuretics, anticonvulsants, topically acting antiglaucoma agents, for antiobesity and anticancer therapies. Herein, a series of chalcone‐based benzenesulfonamides (3a‒m) was synthesized and assessed for its inhibitory...

Microtubules are highly dynamic structures and constitute a crucial component of the cellular cytoskeleton. Besides, Topoisomerases (Topo) play a fundamental role in maintaining the proper structure and organization of DNA. On the other side, dual mechanism drug candidates for cancer treatment primarily aim to enhance the efficacy of cancer treatme...

Garcinia livingstonei T. Anderson (family Clusiaceae) is a rich source of different classes of bioactive compounds, mainly phenolics, which possess beneficial pharmacological activities. In the present study the methanolic extract (ME) of the leaves was analyzed using UPLC-QTOF-MS/MS technique in both negative and positive modes. Its total phenolic...

Even though legumes are valuable medicinal plants with edible seeds that are extensively consumed worldwide, there is little information available on the metabolic variations between different dietary beans and their influence as potential anti-cholinesterase agents. High-resolution liquid chromatography coupled with mass spectrometry in positive a...

Background Organoselenium (OSe) agents and Schiff bases have demonstrated immense potential in the pharmaceutical field due to their broad spectrum of medicinal activities. Methods We herein report the antitumor activities of bis diselenide-based Schiff bases (3a-3c) derived from bis(4-aminophenyl)diselenide 2 and organoselenide-based Schiff bases...

Since the start of the pandemic, considerable advancements have been made in our understanding of the effects of SARS-CoV-2 infection and the associated COVID-19 on the hepatic system. There is a broad range of clinical symptoms for COVID-19. It affects multiple systems and has a dominant lung illness depending on complications. The progression of...

This research work aimed to identify the main components that are responsible for the sedative properties of hop cones and allocate their targets. This investigation was performed through molecular docking, molecular dynamic simulations, root mean square fluctuation (RMSF) analysis, and DFT calculation techniques. The tested compounds from Humulus...

Exploring the sedative properties of natural molecules from hop cones (Humulus lupulus) as promising natural anxiolytics through GABA receptors and the human serotonin transporter

Chromone‐based compounds have established cytotoxic, antiproliferative, antimetastatic, and antiangiogenic effects on various cancer cell types via modulating different molecular targets. Herein, 17 novel chromone‐2‐carboxamide derivatives were synthesized and evaluated for their in vitro anticancer activity against 15 human cancer cell lines. Amon...

A series of tetrahydrobenzo[b]thiophene derivatives was designed and synthesized as dual topoisomerase (Topo) I/II inhibitors implicating potential DNA intercalation. Ethyl‐2‐amino‐3‐cyano‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐4‐carboxylate (1) was prepared by modification of the Gewald reaction procedure using a Fe2O3 nanocatalyst and then it was us...

Organoselenium (OSe) agents hold promise for preventing cancer due to their potential ability to fight cancer development and protect cells from oxidative damage. Herein, OSe-based maleanilic and succinanilic acids were tested to estimate their antitumor activities against fifteen cancer cell lines. Besides, their potential safety and selectivity w...

Herein, we describe the design and synthesis of novel aryl pyrimidine benzenesulfonamides APBSs 5a-n, 6a-c, 7a-b, and 8 as pazopanib analogues to explore new potent and selective inhibitors for the CA IX. All APBSs were examined in vitro for their promising inhibition activity against a small panel of hCAs (isoforms I, II, IX, and XII). The X-ray c...

In this study, novel substituted 1,3,5-triazine candidates (4a-d, 5a-j, and 6a-d) were designed as second-generation small molecules to act as dual IDH1 and IDH2 inhibitors according to the pharmacophoric features of both vorasidenib and enasidenib. Compounds 6a and 6b for leukemia cell lines showed from low to sub-micromolar GI50. Moreover, compou...

The current study aimed to show the seasonal fluctuations’ impact on the composition and bioactivities of the essential oil (EO) of Zanthoxylum piperitum (L.) DC. 'Odorum' (the Odorum) leaves. The four seasons steam-distilled EOs were examined chemically using GC/MS, followed by molecular networking, and tested biologically for antioxidant and an-t...

Although various approaches exist for treating cancer, chemotherapy continues to hold a prominent role in the management of this disease. Besides, microtubules serve as a vital component of the cellular skeleton, playing a pivotal role in the process of cell division making it an attractive target for cancer treatment. Hence, the scope of this work...

Polycystic ovary syndrome (PCOS) is a prevalent endocrinologic and gynecologic disorder that affects women of reproductive age; besides, insulin resistance (IR) occurs in 50–70 % of PCOS cases. Metformin (Met) is commonly prescribed for IR management; however, it does not affect IR with some gastrointestinal symptoms. Spirulina platensis (SP) is a...

Herein, a novel series of naphthamide derivatives has been rationally developed, synthesized, and evaluated for their inhibitory activity against monoamine oxidase (MAO) and cholinesterase (ChE) enzymes. Compared to the reported naphthalene-based hit IV, the new naphthamide hybrids 2a, 2c, 2g and 2h exhibited promising MAO inhibitory activities; wi...

Coenzyme Q10 (CoQ10) occurs naturally in the body and possesses antioxidant and cardioprotective effects. Cardiotoxicity has emerged as a serious effect of the exposure to cadmium (Cd). This study investigated the curative potential of CoQ10 on Cd cardiotoxicity in mice, emphasizing the involvement of oxidative stress (OS) and NF-kB/NLRP3 inflammas...

Broccoli is commonly consumed as food and as medicine. However, comprehensive metabolic profiling of two broccoli varieties, Romanesco broccoli (RB) and purple broccoli (PB), in relation to their anticholinergic activity has not been fully disclosed. A total of 110 compounds were tentatively identified using UPLC-Q-TOF-MS metabolomics. Distinctivel...

Broccoli is commonly consumed as food and as medicine. However, comprehensive metabolic profiling of two broccoli varieties, Romanesco broccoli (RB) and purple broccoli (PB), in relation to their anticholinergic activity has not been fully disclosed. A total of 110 compounds were tentatively identified using UPLC-Q-TOF-MS metabolomics. Distinctivel...

Our study aimed to develop a virucidal throat spray using bioactive compounds and excipients, focusing on the preparation of Curcumin (CUR) in a self-nano emulsifying drug delivery system (SNEDDS). Two molecular docking studies against SARS-CoV-2 targets guided the selection of proper oil, surfactant, co-surfactant, and natural bioactive that would...

Discoidin domain receptor 1 (DDR1) kinase has emerged as a promising target for cancer therapy, and selective DDR1 inhibitors have shown promise as effective therapeutic candidates. Herein, we have identified the first coumarin-based selective DDR1 inhibitors via repurposing of a recent series of carbonic anhydrase inhibitors. Among these, ureidoco...

Selenium (Se) is a crucial micronutrient essential for the human body, playing a critical function in antioxidant protection and immune system function. The chemical and organic properties of organoselenium (OSe) compounds have drawn much attention in medicinal, agrochemical, and materials sciences. OSe compounds have shown superior pharmaceutical...

Directly acting antivirals (DAAs) are a breakthrough in the treatment of HCV. There are controversial reports on their tendency to induce hepatocellular carcinoma (HCC) in HCV patients. Numerous reports have concluded that the HCC is attributed to patient‐related factors while others are inclined to attribute this as a DAA side‐effect. This study a...

Herein, we envisioned the design and synthesis of novel pyrazolopyrimidines (confirmed by elemental analysis, 1 H and 13 C NMR, and mass spectra) as multitarget-directed drug candidates acting as EGFR/TOPO II inhibitors, DNA intercalators, and apoptosis inducers. The target diphenyl-tethered pyrazolopyrimidines were synthesized starting from the re...

Alzheimer’s disease (AD) is the most prevalent form of dementia with cognitive impairment. Genus Cordia has been reported in the treatment of neurodegenerative diseases. We aimed to investigate the total phenolics (TPC), flavonoids (TFC) content and the phenolic composition of leaves of Cordia dichotoma G. Forst. (CDLME) and Cordia sebestena L. (CS...

In this work, the cytotoxicity of monoclonal antibody (Cetuximab, Ce) and Fenbendazole (Fen), as well as their combination therapy were tested with the MTT assay. On the other side, Ce, Fen, and a combination between them were subjected to a colchicine–tubulin binding test, which was conducted and compared to Colchicine as a reference standard. Bes...

Guided by the molecular hybridization principle, a novel series of 4-chloropyridazinoxyphenyl conjugates (3a-h, 4a-e, and 5) was designed and synthesized as proposed apoptotic inducers and PARP-1 inhibitors. The growth inhibition % of the designed hybrids was investigated in eleven cancer cell lines, where the anticancer activities were found to be...

Five known furofuran lignans, dia-sesamin (1), 5-methoxysesamin (2), epi-magnolin (3), kobusin (4) and yangambin (5) were isolated for the first-time from the oleo-gum resin of Commiphora wightii. This is the first report on the 13C NMR assignments for epi-magnolin (3). Each of the isolated compounds was evaluated for its ability to inhibit MIA Pa...

Aim: A novel series of fused benzochromenes with expected cytotoxicity and HIF-1α inhibition was identified. Materials & methods: A bioisosterism-aided approach was applied to design new benzochromenes and assess their cytotoxicity against three cancer cell lines. The probable mechanistic effect and the in silico docking and pharmacokinetic profile...

In the current study, the actinomycetes associated with the red sea‐derived soft coral Sarcophyton glaucum were investigated in terms of biological and chemical diversity. Four different media, M1, ISP2, Marine Agar (MA), and Actinomycete isolation agar (AIA) were used for the isolation of three strains of actinomycetes that were identified as Stre...

Herein, modifications to the previously reported BIBR1591 were conducted to obtain bioisosteric candidates with improved activities. The % inhibition of the newly afforded candidates against the telomerase target was investigated. Notably, 6f achieved superior telomerase inhibition (63.14%) compared to BIBR1532 and BIBR1591 (69.64 and 51.58%, respe...

The consumption of probiotics protects pancreatic β‐cells from oxidative damage, delaying the onset of type 2 diabetes mellitus (T2DM) and preventing microvascular and macrovascular complications. This study aimed to evaluate the antidiabetic activity of CDE fermented by Lactobacillus casei (ATCC 39539) (LC) in alloxan‐induced diabetic rats. The ox...